Chromatin remodelling-related genes (CRRGs) are essential regulators of gene expression and tumour behaviour. Their role in shaping the immune microenvironment and influencing prognosis in ovarian cancer (OV) remains largely unexplored. We develop a CRRG-based prognostic signature and investigate its association with immune infiltration, particularly plasmacytoid dendritic cells (pDCs). We integrated transcriptomic and clinical data from The Cancer Genome Atlas (TCGA; n = 228) and the International Cancer Genome Consortium (ICGC; n = 111) OV cohorts. Differentially expressed CRRGs associated with overall survival were identified and used to construct a prognostic signature via least absolute shrinkage and selection operator and Cox regression. Immune infiltration was analysed using single-sample gene set enrichment analysis (ssGSEA) and validated by multiplex immunofluorescence (mIF). Correlations between CK7+BRD4 expression, pDC infiltration, and chemokine profiles were assessed using public databases and clinical specimens. An 11-gene CRRG-based immune-associated signature was established, effectively stratifying patients into high- and low-risk groups with significantly different overall survival in both cohorts. The risk score was an independent prognostic factor. Immune analyses revealed that high-risk patients exhibited reduced pDC infiltration and lower activation of antigen presentation-related pathways. BRD4 was identified as a key gene negatively correlated with the pDC levels across datasets. High BRD4 expression was associated with poor survival and decreased expression of multiple pDC-attracting chemokines. mIF staining confirmed the inverse correlation between CK7+BRD4 expression and BDCA2+ pDC infiltration in OV tumour tissues. Our study proposes a novel CRRG-based prognostic signature linked to the immune features in OV and highlights BRD4 as a potential regulator of pDC infiltration through the suppression of chemokine expression. These findings provide insights into the interplay between epigenetic regulation and the immune landscape in OV, although the implications for immunotherapy responsiveness warrant further investigation.

Triple-negative breast cancer (TNBC) is a rare and highly metastatic form of cancer. Honokiol (HNK), a biphenolic compound, has been utilized in TNBC treatment, though its specific targets remain unclear. This study aimed to elucidate the effects of HNK on TNBC by combining network pharmacology predictions and experimental validation to uncover its mechanisms. MDA-MB 231 and MDA-MB 468 cells were pre-treated with varying doses of HNK for 24 h. Cell viability, proliferation, and apoptosis were assessed using CCK8 and FACS assays, whereas a wound healing assay was used to evaluate cell migration. A tubule formation assay was used to assess blood vessel formation in HUVECs. Additionally, in vivo activity was confirmed using a zebrafish xenograft model. Network pharmacology and molecular docking predicted active ingredients, key targets, and potential mechanisms of HNK against TNBC. Results indicated that HNK induces apoptosis in MDA-MB 231 and MDA-MB 468 cells and inhibits their migration and proliferation. Furthermore, HNK suppressed blood vessel formation. Zebrafish xenograft experiments validated HNK's inhibitory effect on TNBC cells in vivo. Network pharmacology identified 36 potential HNK targets against TNBC, including HSP90AA1, AKT1, EGFR, ERBB2, HSP90AB1, PGR, MDM2, HDAC1, NR3C1, and MAPK14. Key signaling pathways such as PI3K-Akt, MAPK, Rap1, Ras, and FoxO were implicated in HNK's anti-TNBC mechanism. Molecular docking demonstrated spontaneous interactions between HNK and the targeted proteins. In conclusion, HNK may reduce angiogenesis by blocking the EGFR and HSP90AB1 pathways thereby decreasing proliferation and increasing apoptosis in TNBC cells.

BACKGROUND:Ovarian cancer (OC) remains among the deadliest cancers in women worldwide. Anoikis, a critical process that prevents the establishment of detached cells in non-native sites, is closely associated with cancer cell aggressiveness and poor patient outcomes. Despite its significance, research into the prognostic impact of anoikis-related genes (ARGs) in OC remains scant. METHODS:Single-cell RNA sequencing (scRNA-seq) was adopted to analyze anoikis activity. We used 41 ARGs across distinct cell types for this analysis. The genomic and clinicopathological data was sourced from GSE26712 project (training cohort) and TCGA-OV project (independent validation set), respectively. Cox regression and the least absolute shrinkage and selection operator (LASSO) technique were utilized to develop an anoikis-related risk score (ANRS) for prognosis evaluation. Additionally, the correlation between ANRS and tumor microenvironment (TME) characteristics was explored. Functional experiments were conducted to elucidate the molecular role of the key gene AP1S2 in OC. RESULTS:Survival analyses in both cohorts categorized OC patients into two groups based on the median ANRS. The high-ANRS category exhibited evidently worse survival outcomes. Our findings highlighted a strong link between ARGs and TME characteristics, particularly the stromal components, at both bulk and single-cell transcriptomic levels. This underscores the complex interplay between cancer progression and the tumor-promoting stroma. Additionally, AP1S2 knockdown markedly reduced the proliferative and aggressive capabilities of OC cells. CONCLUSION:The ANRS-derived prognostic tool offers substantial promise for advancing our understanding of OC progression and assisting gynecologists in developing effective treatment strategies for women suffering from this malignancy.

Ovarian cancer (OV) is a highly heterogeneous gynecological tumor that makes the prognostic prediction challenging. Resistance to platinum-based chemotherapy is associated with a poor prognosis in OV. There seems to be an overlap between molecular mechanisms responsible for platinum resistance and immunogenicity in OV. However, the predictive role of platinum resistance-related immune genes for OV prognosis needs to be further explored. In our study, the mRNA expression data of OV patients with corresponding clinical information were collected from The Cancer Genome Atlas (TCGA) cohort and International Cancer Genome Consortium (ICGC) cohort. A multigene signature was constructed for OV patients in the TCGA cohort using the least absolute shrinkage and selection operator (LASSO) Cox regression model according to the optimal value of λ and was validated in the ICGC cohort. Furthermore, we performed functional analysis to explore the immune status between low- and high-risk groups based on the median value of the risk score for the multigene signature. Our data showed that there were 41.1% of the platinum resistance-related genes which differentially expressed between immune score low- and high-OV patients in the TCGA cohort. Univariate Cox regression analysis identified 30 differentially expressed genes (DEGs) associated with overall survival (OS) ( P < 0.05). 14 genes were identified to construct a novel platinum resistance-related immune model for classifying OV patients into the low- and high- risk groups. Patients in the low-risk group showed significantly higher OS than those in the high-risk group ( P < 0.0001 in the both TCGA and ICGC cohort), which was associated with different immune status for the two risk groups. A novel platinum resistance-related immune model can be used for prognostic prediction in OV. Targeting tumor immunity may be a therapeutic alternative for OV with platinum resistance.

Abstract Background & Aims: Given the pivotal role of Zfp36l1b in angiogenesis, proliferation and migration of endothelial cells, we aimed to explore its role in HCC metastasis. Methods: Zfp36l1b expressions in HCC tissues and cells were assessed by qRT-PCR, western blot and immunohistochemistry. The effect of Zfp36l1b on HCC metastasis was studied in vitroand in vivo. Results: Zfp36l1b was frequently down-regulated in HCC and its expression level was significantly associated with aggressive clinicopathological features and overall and disease-free survival of HCC patients after hepatectomy. Loss of Zfp36l1b markedly promoted HCC cells invasion and migration in vitro, and facilitated tumor metastasis in vivo. Conclusions: Zfp36l1b contributes to the development and progression of HCC as an anti-oncogene and may serve as a valuable prognostic marker for HCC patients.

BACKGROUND:Excessive fatty acids in the liver lead to the accumulation of lipotoxic lipids and then cellular stress to further evoke the related disease, like non-alcoholic fatty liver disease (NAFLD). As reported, fatty acid stimulation can cause some specific miRNA dysregulation, which caused us to investigate the relationship between miRNA biogenesis and fatty acid overload. METHODS:Gene expression omnibus (GEO) dataset analysis, miRNA-seq, miRNA cleavage assay, RT-qPCR, western blotting, immunofluorescence and co-immunoprecipitation (co-IP) were used to reveal the change of miRNAs under pathological status and explore the relevant mechanism. High fat, high fructose, high cholesterol (HFHFrHC) diet-fed mice transfected with AAV2/8-shDrosha or AAV2/8-shPRMT5 were established to investigate the in vivo effects of Drosha or PRMT5 on NAFLD phenotype. RESULTS:We discovered that the cleavage of miRNAs was inhibited by analysing miRNA contents and detecting some representative pri-miRNAs in multiple mouse and cell models, which was further verified by the reduction of the Microprocessor activity in the presence of palmitic acid (PA). In vitro, PA could induce Drosha, the core RNase III in the Microprocessor complex, degrading through the proteasome-mediated pathway, while in vivo, knockdown of Drosha significantly promoted NAFLD to develop to a more serious stage. Mechanistically, our results demonstrated that PA can increase the methyltransferase activity of PRMT5 to degrade Drosha through MDM2, a ubiquitin E3 ligase for Drosha. The above results indicated that PRMT5 may be a critical regulator in lipid metabolism during NAFLD, which was confirmed by the knocking down of PRMT5 improved aberrant lipid metabolism in vitro and in vivo. CONCLUSIONS:We first demonstrated the relationship between miRNA dosage and NAFLD and proved that PA can activate the PRMT5-MDM2-Drosha signalling pathway to regulate miRNA biogenesis.

Abstract Ovarian cancer (OC) is identified as one of the most aggressive malignant diseases that imperil women health. Anoikis has been proved to be significantly correlated with the aggressiveness of dislodged cancer cells and poor prognosis of cancer patients. Currently, few researches focus on the prognostic role of anoikis-related genes (AIRGs) on the OC cases. Here, we firstly and systematically analyzed the predictive ability of AIRGS on the prognosis of patients with OC. The genomics data and clinicopathologic information of OC patients were retrieved from TCGA project. Univariate Cox regression and least absolute shrinkage and selection operator (LASSO) method were executed to construct an anoikis–related risk score (AIRS) indicator based on 11 AIRGs. ICGC-OV and GSE26712 were used as independent validation datasets. A nomogram integrated AIRS and pathologic parameters, survival analysis and time-dependent receiver operating characteristic (ROC) curves were utilized to assess the predictive performance of this signature. Successfully, OC patients were divided into two sets based on the optimum cut-off value of risk scores. High risk category evidently suffers from more unfavorable survival outcomes. What is more, AIRS was closely connected with tumor microenvironment (TME) characteristics, mutant landscape, m6A modification and clinical implications. Interestingly, we validated EML2 as a crucial risk gene in OC based on GSEA, single-cell analysis and immunohistochemical staining results. Collectively, AIRS was validated as an independent prognostic indicator with good predictive validity in OC. It can function as a robust clinical parameter which effectively stratifies OC patients and promotes the development of precise medicine.

Tumor cells show deregulated metabolism leading to an enrichment of lactate in the tumor microenvironment (TME). This lactate-rich environment has been reported to impair effector T cells. However, T-regulatory cells (Tregs) show metabolic advantages in lactate-rich TME that maintain a strong suppression of effector T cells, which leads to tumor immune evasion. Therefore, the glycolytic process of tumors could represent a therapeutic target, and agents that modify the energy metabolism of tumor cells have therapeutic potential. Resveratrol is a naturally occurring polyphenol that has been confirmed to suppress tumor cells' glycolytic metabolism. In this study, we show that resveratrol induces metabolic reprogramming in ovarian cancer cells. Resveratrol increases oxidative and decreases glycolysis, in association with decreased lactate production both in vitro and in vivo. Lactate reduction in TME weakens the suppressive function of Tregs, and subsequently restores anti-tumor immunity. Significantly, combined resveratrol and PD-1 blockade promote anti-tumor efficacy. These data suggest that resveratrol's anti-tumor actions in ovarian cancer could be explained, in part, through modification of the anti-tumor immunity, and indicate a novel treatment strategy for improving immune checkpoint blockade therapy using resveratrol.

High-mobility group nucleosome-binding domain 4 (HMGN4) exerts biological functions by regulating gene transcription through binding with nucleosome. As a new epigenetic regulator discovered in 2001, its biological functions have not been clarified. HMGN4 belongs to HMGNs family, in which HMGN1, 2 and 5 have been reported to play roles in oncogenesis of various cancers. However, it is reported that HMGN4 was associated with thyroid and liver cancer. In this study, we discovered for the first time that HMGN4 was highly expressed in human triple-negative breast cancer (TNBC), based on the analysis of the TCGA database. Moreover, we found that HMGN4 controlled the proliferation of human TNBC cells both in vitro and in vivo. Mechanistically, the positive correlation occurred between HMGN4 and STAT3 downstream genes while HMGN4 played an indispensable role in constitutively active STAT3 (STAT3C) induced colony formation. Interestingly, we reported that STAT3 regulated HMGN4 transcription as its transcriptional factor by chromatin immunoprecipitation and HMGN4 promoter-luc assays. That is to say, there is a feed-forward signaling circuit between HMGN4 and STAT3, which might control TNBC cell growth. Finally, we proved that the interference of HMGN4 by nanovehicle-packaged siRNA may be a potentially effective approach in TNBC treatment. In summary, our findings not only identified a novel regulator in TNBC cell proliferation but also revealed the mechanism by which HMGN4 acted as a downstream gene of STAT3 to participate in the STAT3 pathway, which indicated that HMGN4 was likely to be a potential novel target for anti-TNBC therapy.

Purpose Aberrant activation of STAT3 signal pathway promotes tumor progression in many solid tumor types, including cervical cancer and endometrial cancer. BBI608, the STAT3 inhibitor had been reported in previous studies for restraining cancer stem cells. However, whether BBI608 is available for inhibiting the proliferation of cervical cancer or endometrial cancer remains poorly understood. This study investigated the anti-tumor effect and molecular mechanism of BBI608 on the patient-specific primary cells (PSPC) generated from cervical and endometrial cancer in vitro. Methods PSPCs were obtained from four patients via biopsy. The cell viability was analyzed by the CCK8 assay. The PSPCs were treated with various concentrations of BBI608 or/and paclitaxel; and then, western blot was applied to investigate the expression of phosphorylated STAT3 (pSTAT3). Results The PSPCs cell viability was reduced after treated with BBI608 at a lower concentration. Western blot results showed a reduction trend of pSTAT3 after PSPCs treated with BBI608. Our results demonstrated that BBI608 at the certain concentrations worked well in reducing the cell viability of PSPC from the patients who suffered from cervical cancer and endometrial cancer. Conclusions In this study, the patient-specific primary cell (PSPC) was used as the pre-clinical model for investigating the efficiency of BBI608 in reducing cancer cells viability. BBI608, at a clinical-relevant concentration, had valid efficiency in PSPCs from the patients. The dose of drugs treatment and the measured results were more valuable for further guiding clinical trials.

Abstract Background Poly-GA, a dipeptide repeat protein unconventionally translated from GGGGCC repeat expansions in C9orf72, is abundant in C9orf72-related amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Although the poly-GA aggregates have been identified in C9orf72-ALS/FTD neurons, the effects on UPS and autophagy, and their exact molecular mechanisms have not been fully elucidated. Methods We generated poly-GA mice,and treated poly-GA mice for 90 days by intraperitoneal injection rapamycin (4 mg/kg) every 2 days until behavioral analysis. GFAP (an astrogliosis marker), Iba1 (a microgliosis marker), GFP, p62, p-p62 (S349), p-p62 (S403) and LC3 proteins expression were quantified in brain tissues by immunohistochemistry, immunofluorescence, immunoblotting. These results were validated in vitro by protein mass spectrometry, co-immunoprecipitation and immunofluorescence. Results Herein, our in vivo experiments show that ploy-GA mice expressing 150 repeats but not 30 repeats GA exhibit significant aggregates in cells, behavioral deficits, and activate autophagy in the brain, in vitro results demonstrate that aggregated poly-GA induces proteasomal stress through directly binding proteasome subunit PSMD2 to recruit proteasome and impair its function, subsequently activates phosphorylation and ubiquitination of p62 to recruit autophagosome, ultimately leading to compensatory autophagy activation. While rapamycin treatment significantly improves the degenerative symptoms of mice expressing 150 repeats poly-GA, relieves neuronal injury and reduces neuroinflammation and aggregates in the brain. Conclusion In summary, we clarify for the first time the relationship of poly-GA between proteasome and autophagy: poly-GA aggregates recruit autophagosomes only when it forms complex with the proteasome and causes proteasomal stress. Our study provides support for further promoting the comprehension about the pathogenesis of C9orf72 and may bring a hint for the therapy.

It has been reported that chemotherapy resistance mainly contributed to treatment failure and poor survival in patients with ovarian cancer. Therefore, clarifying the molecular mechanism and identifying effective strategies to overcome drug resistance may play an important clinical impact on this malignant tumor. In our study, we found that the expression of Glycosyltransferase 8 domain containing 2 (GLT8D2) was significantly upregulated in ovarian cancer samples with CDDP (Cis-dichlorodiammine-platinum) resistance. Biological experiment demonstrate that GLT8D2 overexpression confers CDDP resistance on ovarian cancer cells; however, inhibition of GLT8D2 sensitized ovarian cancer cell lines to CDDP cytotoxicity both in vitro and in vivo. By using affinity purification/mass spectrometry (IP/MS) and reciprocal co-immunoprecipitation (co-IP) analyses, we found that GLT8D2 interacts with fibroblast growth factor receptor 1(FGFR1) in ovarian cancer cells. Furthermore, overexpression of GLT8D2 activated FGFR/PI3K signaling axis and upregulated the phosphorylation levels of FRS2a and AKT (AKT serine/threonine kinase). Importantly, pharmacological inhibition of FGFR and PI3K (phosphatidylinositol 3-kinase) signaling pathway significantly counteracted GLT8D2-induced chemoresistance and enhanced platinum's therapeutic efficacy in ovarian cancer. Therefore, our findings suggest that GLT8D2 is a potential therapeutic target for the treatment of ovarian cancer; targeting GLT8D2/FGFR/PI3K/AKT signaling axis may represent a promising strategy to enhance platinum response in patients with chemoresistant ovarian cancer.

OBJECTIVE:To explore the mechanism underlying the regulation of long non-coding RNA (LncRNA) ACTA2-AS1 on CXCL2 as a ceRNA of miR-532-5p in the progression of ovarian cancer (OC).METHODS:A qRT-PCR assay was carried out for analyzing the expression changes of ACTA2-AS1, miR-532-5p, as well as CXCL2 in OC tissues and corresponding healthy paracancerous tissues HOSEpiC (human ovarian epithelial cells), and OC cells. OC cells were grouped and transfected, and the fluorescent in situ hybridization was adopted for evaluating ACTA2-AS1 in the cells. Additionally, a dual luciferase reporter (DLR) assay was carried out for verifying the correlation of ACTA2-AS1 with miR-532-5p and of miR-532-5p with CXCL2. Cells were transfected with si-ACTA2-AS1, miR-532-5p, or CXCL2 overexpression plasmids, and then the cell proliferation, invasion, and apoptosis were determined using MTT, Transwell, and flow cytometry assays, respectively.RESULTS:Compared with paracancerous tissues and HOSEpiC cells, OC tissues and cells showed increased ACTA2-AS1 and CXCL2 expression and decreased miR-532-5p expression (all P<0.05). ACTA2-AS1 acted as ceRNA in OC by negatively regulating miR-532-5p. Additionally, upregulating ACTA2-AS1 intensified the proliferation and invasion of cancer cells and suppressed their apoptosis (all P<0.05), and inhibition of it resulted in opposite results. In contrast, overexpressing miR-532-5p suppressed the proliferation, invasion, and clone formation of the cells and promoted their apoptosis (all P<0.05). The effect of ACTA2-AS1 on OC cells can be partially reversed by overexpressing miR-532-5p. Moreover, CXCL2, positively correlated with ACTA2-AS1 in expression (P<0.0001, r=0.7385), was the target of miR-532-5p, and its overexpression could partially offset the influence of miR-532-5p on OC cells.CONCLUSION:LncRNA ACTA2-AS1 can act as a tumor promoter in OC by absorbing miR-532-5p as ceRNA and regulating CXCL2, and ACTA2-AS1 inhibitor is expected to play a role in targeted therapy of OC.

Growing evidence suggests that microbes can influence the onset of cancer and its consequent development. By researching samples from patients afflicted by cervical cancer, we aimed to explore the associated dynamics and prognostic value of intratumoral levels of F. nucleatum. We used qPCR to analyze tumor tissues obtained from 112 cervical cancer patients in order to characterize the levels and influences of intratumoral levels of the F. nucleatum. Especially for recurrent tissues, there was a distinct observation of higher levels of F. nucleatum in cervical cancer. Patients with high burdens of F. nucleatum intratumoral infiltration exhibited correspondingly poor rates of both overall survival and progression-free survival. Measures of the levels of F. nucleatum were found to have been reliable independent prognostic factors that could predict rates of PFS for afflicted patients (HR = 4.8, 95%CI = 1.2-18.6, P = 0.024). Notably, the levels ofF. nucleatum were positively correlated with tumor differentiation. Cancer cells from patients with relatively high levels of F. nucleatum were observed to possess the characteristics of cancer stem cells (CSCs). We propose that F. nucleatum might be one potential cervical cancer diagnostic and prognostic biomarker, and these findings will help to provide a sound rationale and merit for further study of this bacterium.

MYO10, recognized as an important regulator of cytoskeleton remodeling, has been reported to be associated with tumorigenesis. However, its functional implication in cervical cancer and potential mechanism still remain to be undetermined currently. MYO10 level in cervical cancer tissues was analyzed by using data retrieved from The Cancer Genome Atlas and ONCOMINE databases. Messenger RNA and protein expression levels were determined by quantitative real-time polymerase chain reaction and Western blotting. Small-interfering RNA and overexpressing plasmid were used for MYO10 silencing and overexpression, and cell proliferation was analyzed by CCK-8. Transwell assays were performed to investigate the ability of cell migration and invasion. MYO10 was upregulated in cervical cancer tissues and cells when compared to normal controls, and survival analysis showed patients with high MYO10 expression had worse overall survival. Moreover, knockdown/overexpression of MYO10 significantly inhibited/enhanced the proliferation, invasion, and migration capabilities of cervical cells transfected with siRNAs/overexpressing plasmid. Additionally, MYO10 silencing inhibited PI3K/Akt signaling pathway by decreasing the phosphorylation status of PI3K and AKT. Data from the present study indicated that MYO10 were overexpressed in patients with cervical cancer and positively linked with poor prognosis. Experimental results suggested that MYO10 induced a significant encouraging effect in cervical cancer cell proliferation, invasion, and migration, linked with involvement of PI3K/Akt signaling. Collectively, these results emphasize a novel role for MYO10 overexpression in cervical cancer and provide a potent therapeutic strategy against cervical cancer.

Chemotherapeutic treatments against hepatocellular carcinoma (HCC) are necessary for both inoperable patients to improve prospects for survival and surgery patients to improve the outcome after surgical resection. However, multidrug resistance (MDR) is a major obstacle to obtaining desirable results. Currently, increasing the chemotherapy sensitivity of tumor cells or discovering novel tumor inhibitors is an effective therapeutic strategy to solve this issue. In the present study, we uncovered the dual-inhibitory effect of miR-338-5p: on the one hand, it could downregulate ABCB1 expression and sensitize HCC cells to doxorubicin and vinblastine by directly targeting the 3'-untranslated region (3'-UTR) of ABCB1, while, on the other hand, it could suppress the proliferation of HCC cells by directly targeting the 3'-UTR of EGFR and reducing EGFR expression. Since EGFR regulates ABCB1 levels, the indirect action of miR-338-5p in ABCB1 modulation was revealed, in which miR-338-5p inhibits ABCB1 expression by targeting the EGFR/ERK1/2 signaling pathway. These data indicate that the miR-338-5p/EGFR/ABCB1 regulatory loop plays a critical role in HCC, and a negative correlation between miR-338-5p and EGFR or ABCB1 was also detected in HCC clinical samples. In conclusion, these findings reveal a critical role for miR-338-5p in the regulation of MDR and proliferation of HCC, suggesting the potential therapeutic implications of miR-338-5p in HCC treatment.

OBJECTIVE:To investigate the allo-NK cell-mediated killing effect enhanced by decitabine on leukemia stem cells(LSC) and the underlying mechanisms.METHODS:LSC were separated from KG1a cells by using immunomagnetic beads. Allo-NK cells were isolated and purified from PBMC of healthy donors. Cytotoxicity of allo-NK cells against LSC were measured by LDH releasing assay. The apoptosis induced by allo-NK cells in LSC and the expressions of NKG2D ligands including MICA/B and ULBP1-3 on LSC were detected by flow cytometry.RESULTS:The killing rate of allo-NK cells to LSC treated with 10 µmol/L decitabine for 24 hours was significant higher than that to LSC without treatment(60.52%±3.52% vs 22.08%±2.07%, 73.93%±2.33% vs 28. 99%±3.13%, 83.08%±1.32% vs 36.44%±2.40%, respectively)at the effector-target ratios of 5:1, 10:1, 20:1 (P<0.05). At the effector-target ratio of 10:1, decitabine significantly enhanced the apoptosis of LSC induced by allo-NK cells (7.84%±0.34% vs 3.33%±0.64%)(P<0.05). The expressions of NKG2D ligands(MICA/B,ULBP1,ULBP2,ULBP3) on LSC treated with decitabine 10 µmol/L for 24 hours were significantly increased (P<0.05).CONCLUSION:Decitabine may enhance the allo-NK cell-mediated killing effects on LSC by up-regulation of the expressions of NKG2D ligands on LSC.

To investigate the effect of lidamycin (LDM) on human gastric carcinoma BGC823 cells and xenograft growth in nude mice, MTT (methyl thiazolyl tetrazolium) assay was used to determine the inhibition of BGC823 cell proliferation by LDM. Induction of apoptosis was studied by flow cytometry and TUNEL assay. The expression of VEGF was detected by Western blotting analysis. Athymic nude mice were used to determine in vivo antitumor activity. Proliferation inhibition and apoptosis induction were studied in lidamycin-treated cells. The expression of VEGF in BGC823 cells decreased in a dose-dependent manner. LDM at 0.02 mg x kg(-1) and 0.04 mg x kg(-1) suppressed the growth of BGC823 xenografts in nude mice by 57% and 72%, respectively. LDM potently induces apoptosis in human gastric carcinoma BGC823 cells and inhibits xenograft growth.