Thoracoscopic segmentectomy is the main surgical method for the treatment of earlylung cancer. With the promotion of technology and increasingly accurate criteria for lung subsegments, lung nodules with complex positions involving intersegmental and multisegments have become technical bottlenecks. This study aimed to verify whether seeking anatomical conditions for creating a fissure by tunneling techniques with precise resection of lung segments could solve this bottleneck problem. The clinical data of patients with lung nodules ≤ 2 cm located in the complex position in the Department of Thoracic Surgery of Jiangsu Provincial People's Hospital from January 2019 to August 2023 were collected. Date analyzed the characteristics of patients who underwent seeking anatomical conditions for creating a fissure by tunneling techniques with precise resection of lung segments (segment group) at complex setting and compared the surgical outcomes and complications between these lobectomy patients (lobectomy group) at similar locations. A total of 22 patients were included segment group and 47 patients were included lobectomy group. Except for the depth ratio or tumor size or consolidation tumor ratio (CTR), there were no significant differences in the other baseline data between the two groups. All patients in segment group received a satisfactory surgical margin. Compared to the lobectomy group, surgical outcomes were better in segment group (p < 0.05 for postoperative hospital stay and the counts of resected subsegments). Seeking anatomical conditions for creating a fissure by tunneling techniques is a promising technique for performing precise resection of lung segments with a safe resection margin for patients with lung nodules at complex positions involving multiple segments. It can be used as a precise resection of lung segments technique.

Background Thoracoscopic segmentectomy is the main surgical method for the treatment of early lung cancer. With the promotion of technology and increasingly accurate criteria for lung subsegments, lung nodules with complex positions involving intersegmental and multisegments have become technical bottlenecks. This study aimed to verify whether lobar split cone-shaped subsegmentectomy could solve this bottleneck problem. Methods The clinical data of patients with lung nodules ≤ 2 cm located in the complex position in the Department of Thoracic Surgery of Jiangsu Provincial People's Hospital from January 2019 to August 2023 were collected. We analyzed the characteristics of patients who underwent lobar split cone-shaped subsegmentectomy and compared the surgical outcomes and complications between these patients and lobectomy patients at similar locations. Results A total of 22 patients underwent lobar split cone-shaped subsegmentectomy, and 47 patients were treated with lobectomy. Lobar split cone-shaped subsegmentectomy for patients with lung nodules in complex positions can yield satisfactory surgical margins under some conditions (in this study, the nodule diameter was 0.98 ± 0.31 mm, the depth ratio was 0.43 ± 0.13, and the consolidation tumor ratio was 0.27 ± 0.19). Compared to those in the lobectomy group, surgical outcomes were better (p > 0.05 for surgical complications and p < 0.05 for postoperative hospital stay and the number of resected subsegments). Conclusion Lobar split cone-shaped subsegmentectomy is a promising method for performing true lung segmentectomy with safe resection margins for patients with lung nodules in complex positions involving multiple segments. It can be used as a true lung segmentectomy method.

Background: Esophageal squamous cell carcinoma (ESCC) is a major subtype of esophageal cancers. The five-year survival rate of ESCC is low, and molecular targets for ESCC treatment and prognosis assessment are very limited. T cells are critical for the clearance of cancer cells, and blockade of co-inhibitory molecules for T cell activation has emerged as a promising therapy to treat cancer patients. However, in ESCC patients, co-inhibitory molecules regulating T cell activation are poorly documented. Objective: We aim to evaluate how the presence of inhibitory check-point molecules in T cells could impact the survival of patients. Methods: We performed a follow-up study of 161 patients undergoing resection of esophageal carcinoma from February 2014 to December 2015, by immunohistochemical staining of six co-inhibitory molecules for T cell activation, namely PD-1, CTLA-4, TIM-3, LAG-3, BTLA and A2AR. Expression of each of the six co-inhibitory molecules was analyzed for its correlation with patient survival by Kaplan-Meier survival analysis. We also applied Kaplan-Meier analyses to evaluate the concomitant expression of co-inhibitory molecules and their correlation with patient survival. Results: We found that levels of PD-1, TIM-3 and BTLA can be used as independent prognostic factors for the overall survival of patients with ESCC. More importantly, our study found that the co-expression of PD-1 and TIM-3, PD-1 and BTLA, TIM-3 and BTLA significantly reduced the survival of patients with ESCC (P<0.05). Conclusion: Therefore, our results suggest the necessity of evaluating the tumor tissue expression of co-inhibitory molecules and targeting co-expressed molecules in immunotherapies for ESCC patients.

FAM107A may have a dual role in regulating the biological functions of tumors; however, its role in prostate adenocarcinoma (PRAD) remains unknown. We analyzed FAM107A expression by employing databases to clarify its potential prognostic value for PRAD, as well as its role in the pathogenesis of PRAD. We observed that the FAM107A expression level is decreased in PRAD, and the reduced expression is considerably associated with poor overall survival and progression-free survival (PFS). To explore the mechanism of FAN107A in PRAD, we performed an immune cell infiltration analysis and a gene set enrichment analysis. The results showed that FAM107A expression is positively related to mast cells and natural killer cells. The Wnt signaling pathway, the MAPK signaling pathway, and the immune responses are differentially enriched in the FAM107A high-expression phenotype. The FAM107A low-expression phenotype is linked to apoptosis-induced DNA fragmentation and DNA methylation in PRAD. To assess the relationship between the clinical features and the FAM107A expression, we performed a logistic regression analysis and observed that a decreased FAM107A expression is associated with poor prognostic features, including the T stage, the N stage, the Gleason score, residual tumors, and the TP53 status. Our multivariate Cox regression results showed that the Gleason score, the primary therapy outcome, and the FAM107A expression are independent prognostic factors in PFS. In summary, we consider FAM107A an independent risk factor for PFS in PRAD. Moreover, several pathways may reveal the role of FAM107A in triggering carcinogenesis. These discoveries provide novel perspectives for future research to elucidate the pathogenic mechanism underlying PRAD.

Ethnopharmacological relevance: Astragalus mongholicus, Solanum nigrum Linn, Lotus plumule, Ligusticum are widely used traditional herbal medicines for cancer treatment in China. They were typical drugs selected from Gubenyiliu II and series of formula (GYII), which were developed on the foundation of YIQIHUOXUEJIEDU theory. In the present study, four active ingredients (Astragaloside IV, alpha-solanine, neferine, and 2,3,5,6-tetramethylpyrazine) derived from medicines above were applied in combination as SANT. Aim of the study: Triple-negative breast cancer (TNBC) is a serious threat to women's health worldwide. Heparanase (HPSE) is often up-regulated in breast cancer with the properties of facilitating tumorigenesis and influencing the autophagy process in cancer cells. This study aimed at evaluating the anti-tumor potential of SANT in treating HPSE related TNBC both in-vitro and in-vivo. Materials and methods: In this study, we explored the correlation between HPSE expression and survival of breast cancer patients in databases. We performed MTS, trans-well and wound scratch assays to assess the impact of SANT on cell proliferation and migration. Confocal microscopy observation and western blots were applied to verify the autophagy flux induced by SANT. Mice models were employed to evaluate the efficacy and safety of SANT in-vivo by tumor weights and volumes or serum index, respectively. To analyze the underlying mechanisms of SANT, we conducted human autophagy PCR array and angiogenesis proteome profiler on tumor tissues. Results: Patients with elevated HPSE expression were associated with a poor outcome in both RFS (P = 1.7e-12) and OS (P = 0.00016). SANT administration significantly inhibited cancer cells' proliferation and migration, enhanced autophagy flux, and slightly reduced the active form of HPSE in-vitro. SANT also suppressed tumor growth and angiogenesis in-vivo. Human autophagy PCR array results indicated that SANT increased the ATG16L1, ATG9B, ATG4D gene expressions while decreased TMEM74 and TNF gene expressions.Angiogenesis proteome profiler results showed SANT reduced protein level of HB-EGF, thrombospondin-2, amphiregulin, leptin, IGFBP-9, EGF, coagulation factor III, and MMP-9 (pro and active form) in tumor, raised the protein expression of serpin E1 and platelet factor 4. Conclusions: These findings indicated that herbal compounds SANT may be a promising candidate in anti-cancer drug discovery. It also provides novel strategies for using natural compounds to achieve optimized effect.

OBJECTIVE:To systematically explore the pharmacological mechanism of Radix Paeoniae Rubra (RPR) against lung cancer (LC).METHODS:A network pharmacology approach, which involves active ingredients and target forecast, network construction, gene ontology and pathway enrichment, was employed in this research. In addition, the effect of Baicalein (BAI) in RPR on A549 cells was researched in vitro and in vivo.RESULTS:A total of 159 targets of the 29 active components in RPR were procured by pharmacokinetic parameters. The network analysis showed that β-sitosterol, baicalein, (+)-catechin, ellagic acid, stigmasterol, (2R, 3R)-4-methoxyl-distylin were the main ingredients and JUN, VEGFA, BCL2 were the hub targets of RPR in the treatment of LC. The functional enrichment analysis showed that RPR likely was useful to LC by regulating numerous pathways including Pathways in cancer, MAPK signaling pathway and so on. MTT results showed that 100μM, 200μM, 400μM of BAI had a time and dose-dependent inhibitory effect on A549 cells proliferation; Wound healing and transwell assays showed that 100μM, 200μM, 400μM of BAI could significantly restrain the migration and invasion of A549 cells; Flow cytometry assay results showed that 100μM, 200μM, 400μM of BAI could induce apoptosis of A549 cells. In vivo, BAI (50, 100 mg/kg) significantly inhibited tumor growth and promoted apoptosis of tumor cells compared with the control group.CONCLUSION:BAI in RPR may exert anti-tumor effects by inhibiting the proliferation, migration and invasion of LC cells, and inducing the apoptosis of LC cells.

半枝莲和白花蛇舌草是癌症治疗当中常用的清热解毒中药,在中医临床遣方用药当中常相须配伍使用.近些年,陆续有中医药研究团队展开对此药对的研究,随着现代研究手段的进步,研究内容也从临床病案的总结观察逐步深入到基础实验机制的挖掘和探讨,在主治功效、剂型和成分、比例和用量、作用机制以及中医理论探讨等方面均有涉及.现将所报道的研究进行综述,旨在梳理半枝莲和白花蛇舌草药对研究现状,为更加深入的研究和探讨做铺垫.

OBJECTIVE:To study the mechanism of Huayu Wan on the metastasis of Lewis lung cancer in mice via the platelet pathway.METHOD:Construction of the lung metastasis model by injection of Lewis cells through the tail vein. The next day, 72 mice were randomly divided into the Huayu Wan group (HYW), the aspirin group, the control group, and the normal group . Treatment was given for 5 days per week for a total of 16 days. The size and distribution of lung metastases were observed. Thromboelastography was used to detect platelet function, flow cytometry was used to analyze platelet activation, and ELISA was used to detect platelet tumor metastasis-related factor expression.RESULT:Lung weight in the control group was significantly higher than that in the HYW group (P < 0.05). The distribution of lung metastases in the control group was obviously more than that in the HYW group. The thromboelastogram showed that the R value of the control group was significantly lower than the normal group, while the R values of the HYW and aspirin groups were higher than the control group (P < 0.05). Flow cytometry analysis showed that the expression of CD62P in platelet-rich plasma in the control group was significantly higher than that in the normal group, while the expression of CD62P in the HYW and aspirin groups was lower than that in the control group (P < 0.05). In addition, ELISA showed that the expression of VEGF, bFGF, and CD62P in serum of the HYW group was significantly decreased than the control group (P < 0.05), and the expression of VEGF and bFGF in serum of the aspirin group was significantly decreased than the control group (P < 0.05).CONCLUSION:The mechanism of Huayu Wan inhibiting the metastasis of lung cancer in mice may be related to the improvement of blood hypercoagulability, the inhibition of platelet activation, and the expression of VEGF, bFGF, and CD62P.

目的:综述中药赤芍活性成分抗肿瘤的作用机制,为其临床应用提供参考.方法:以"赤芍""活性成分""肿瘤""作用机制""Paeoniae Radix Rubra""Active constituent""Cancer""Mechanism"等为中英文关键词,在PubMed、中国知网、万方等数据库中组合查询2009年1月-2019年1月发表的相关文献,对赤芍活性成分抗肿瘤作用机制的研究进行归纳总结.结果与结论:共检索到相关文献近100篇,其中有效文献41篇.赤芍活性成分对于肺癌、乳腺癌、胃癌、胰腺癌、宫颈癌、肠癌、肝癌、骨肉瘤等肿瘤细胞均具有广泛的抑制作用,其主要通过抑制肿瘤细胞增殖/侵袭和转移、诱导肿瘤细胞凋亡、调节机体免疫功能、逆转肿瘤细胞多耐药性、抑制血管生成等多种途径发挥抗肿瘤作用.但是,当前赤芍抗肿瘤研究多以体外研究为主,并不能充分阐释赤芍活性成分的抗肿瘤作用机制;此外,活性成分也多局限于皂苷类.建议可借助网络药理学的方法,构建药材成分与疾病靶点相互作用网络,挖掘重要靶点及相关分子通路,并通过体内外研究进一步明确赤芍及其有效成分抗肿瘤的作用机制,为临床应用赤芍及相应成分治疗肿瘤提供可靠的理论依据和科学基础.

Objective:To study the effect and mechanism of Huayu Wan in combination of chemotherapy of tumor treatment.Methods:HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the effificacy of doxorubicin was studied.Results:HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P<0.01). Furthermore, HYW improved drug delivery of doxorubicin to tumor tissues, and this activity was associated with HYW-induced microvascular proliferation (P<0.01).Conclusions:HYW can promote microangiogenesis and increase blood supply in tumor tissues, which in turn may increase the risk of metastasis. At the same time, HYW increases drug delivery and improves the effificacy of chemotherapy drugs through vascular proliferation. Therefore, rational judgment must be exercised when considering applying HYW to an antitumor regimen.

Triple-negative breast cancer (TNBC), which is characterized by inherently aggressive behavior and lack of recognized molecular targets for therapy, poses a serious threat to women's health worldwide. However, targeted treatments have yet to be made available. A crosstalk between tumor cells and platelets (PLT) contributing to growth, angiogenesis and metastasis has been reported in numerous cancers. Heparanase (Hpa), the only mammalian endoglycosidase that cleaves heparan sulfate, has been demonstrated to contribute to the growth, angiogenesis and metastasis of numerous cancers. Hypoxia affects the growth, angiogenesis and metastasis of nearly all solid tumors, and the ability of Hpa to promote invasion is enhanced in hypoxia. However, whether Hpa can strengthen the crosstalk between tumor cells and PLT, and whether enhancing the biological function of Hpa in TNBC promotes malignant progression, have yet to be fully elucidated. The present study, based on bioinformatics analysis and experimental studies in vivo and in vitro, demonstrated that Hpa enhanced the crosstalk between TNBC cells and PLT to increase the supply of oxygen and nutrients, while also conferring tolerance of TNBC cells to oxygen and nutrient shortage, both of which are important for overcoming the stress of hypoxia and nutritional deprivation in the tumor microenvironment, thereby promoting malignant progression, including growth, angiogenesis and metastasis in TNBC. In addition, the hypoxia-inducible factor-1a (HIF-1a)/vascular endothelial growth factor-a (VEGF- a)/phosphorylated protein kinase B (p-)Akt axis may be the key pathway involved in the effects of Hpa on the biological processes mentioned above. Therefore, improving local hypoxia, anti-Hpa treatment and inhibiting PLT activation may improve the prognosis of TNBC.

Abstract BackgroundBiomarkers which can robustly predict the recurrence of stage II colorectal cancer (CRC) have been urgent needed. Immune cells highly related to the recurrence and prognosis of CRC. However, whether the immune cells take part in the recurrence of stage II CRC has not known.MethodsExplored the roles and possible mechanism of immune cells in the recurrence of stage II CRC by public databases.ResultsTumor Immune Estimation Resource (TIMER) analysis indicated the macrophage infiltration level in stage II CRC: Significantly higher in the nonrecurrence group than that in the recurrence group; Significantly negative correlated with the recurrence-related hub gene transferrin (TF); Significantly positive correlated with the improved disease-free survival (DFS) and overall survival (OS). And macrophage infiltration related-gene recurrent model (GRM) (area under the curve (AUC) = 0.906) provide a better performance than the GRM established previously (AUC = 0.882) to predict the recurrence of stage II CRC. Gene Set Enrichment Analysis (GSEA) analysis indicated macrophage (M1) infiltrated in the tumor microenvironment (TME) defending against recurrence as a dynamic process: M1 was activated by receiving the stimulus signals (LPS/IFN- γ) which released by CRC cells, then infiltrating and recognizing the tumor to secrete IL-6 to directly or indirectly act on TF or create anti-tumor TME to kill tumor cells.ConclusionsThis study maybe provides a novel immunological perspective to explore the mechanism of recurrence and improve clinical practice performance in stage II CRC.

ETHNOPHARMACOLOGICAL RELEVANCE:The Scutellaria barbata and Hedyotis diffusa (SH) herb pair is extensively used in Traditional Chinese Medicine for efficacy enhancement in cancer treatment in China and Asian countries. Superior clinical efficacy observations based on high dosages (≥60 g) motivated us to explore appropriate dosages and the underlying mechanisms of action. AIM OF THE STUDY:To explore the efficacy and potential mechanisms of actions of SH through in vitro and in vivo experiments and network pharmacology. MATERIALS AND METHODS:SH lyophilized powder (SHLP) was prepared from decoctions and the active ingredients were identified using high performance liquid chromatography (HPLC). Proliferation and migration experiments in vitro and tumor growth in vivo were performed to evaluate the effects of SHLP on breast cancer. Corresponding potential target genes for SHLP components and breast cancer were extracted from established databases and the Protein-Protein Internetwork of shared genes were constructed using STRING database. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation clusters were acquired and the top 30 pathways were presented. At last, as one of pathways indicated by enriched results, apoptosis was validated with flow cytometric analysis and caspase-3, 8, 9 activities. RESULTS:Seventy-five ingredients were identified from SHLP by HPLC. High SHLP doses inhibited proliferation and migration of three types of breast cancer cells in vitro and tumor growth in nude mice. After target genes extraction and intersection, the top 30 KEGG clusters were enriched, including PI3K-Akt, cell cycle and other related pathways like VEGF, Micro-RNAs and NF-κB, besides, key genes in apoptosis were mapped. In the last, apoptosis was validated by flow cytometric analysis and caspase-3, 8, 9 activities after SHLP treatment. CONCLUSION:High SHLP dosages inhibited breast cancer in vitro and in vivo, enriched by network pharmacology and confirmed by flow cytometric analysis and caspase activation, with apoptosis was identified as one of the mechanisms of action of SHLP. SHLP administration with higher doses is recommended for clinical usage.

ETHNOPHARMACOLOGICAL RELEVANCE:Dahuang Zhechong pill (DHZCP) is a commonly used traditional Chinese medicine for the treatment of hepatocarcinoma.AIM OF THE STUDY:Previous studies have found that DHZCP can exert anti-hepatocarcinoma effects and reverse drug resistance by inhibiting energy metabolism. The goal of this study was to further explore the pharmacodynamic substances that inhibit energy metabolism.METHODS:The components of DHZCP absorbed into plasma were identified by UHPLC-Q-TOF-MS/MS. The Swiss and STITCH databases were used for target collection. The DAVID database was used for pathway enrichment analysis. Cytoscape software was used for network construction. The CCK-8 method detected cell viability. Chemiluminescence was used to detect ATP levels.RESULTS:A total of 89 components absorbed into plasma were identified by UHPLC-Q-TOF-MS/MS. Based on this, 24 potential pharmacodynamic substances were selected by network pharmacology. Among them, 11 components such as rhein can significantly inhibit ATP levels.CONCLUSIONS:Rhein, emodin, chrysophanol, hypoxanthine, baicalein, baicalin, wogonoside, acteoside, formononetin, isoliquiritigenin, and glycyrrhizic acid were the pharmacodynamic substances responsible for inhibition of energy metabolism of DHZCP.

A proper animal model is crucial for a better understanding of diseases. Animal models established by different methods (subcutaneous injections, xenografts, genetic manipulation, chemical reagents induction, etc.) have various pathological characters and play important roles in investigating certain aspects of diseases. Although no single model can totally mimic the whole human disease progression, orthotopic organs disease models with a proper stromal environment play an irreplaceable role in understanding diseases and screening for potential drugs. In this article, we describe how to implant breast cancer cells into the mammary fat pad in a simple, less invasive, and easy-to-handle way, and follow the metastasis to distant organs. With the proper features of primary tumor growth, breast and nipple pathological changes, and a high occurrence of other organs' metastasis, this model maximumly mimics human breast cancer progression. Primary tumor growth in situ, long-distant metastasis, and the tumor microenvironment of breast cancer can be investigated by using this model.

Dahuang Zhechong Pill (DHZCP) has been widely used in the treatment of hepatocarcinoma in China. The aim of our study was to identify the characteristic components of DHZCP. First, HPLC fingerprint of DHZCP was established to analyze the common components of 14 batches of DHZCP samples, which were purchased from different manufacturers. The results of HPLC fingerprint detected 164 peaks in these 14 batches of DHZCP. Through similarity analysis, cluster analysis, and principal component analysis, we identified 20 common components upon which to conduct quantitative analysis conducted by an HPLC method. After that, a cytotoxicity test was carried out to screen the active components in DHZCP. The results showed that hypoxanthine, rhein, emodin, aloe emodin, and wogonin are the active components of DHZCP for the treatment of hepatocarcinoma, as they have significant inhibitory effect against the activity of drug-resistant hepatocarcinoma cells (SMMC-7721/DOX) than others.

张仲景在《金匮要略》中创制的大黄(庶)虫丸是有效的抗癌中成药方,适用于肝癌、胃癌、食道癌、肺癌、胰腺癌、白血病以及宫颈癌、子宫肌瘤等,能显著提高患者生活质量,减缓肿瘤的发展.本文整理分析了其在抗癌症治疗中的基础及临床研究概况,综述其抗肿瘤机制研究进展,并结合本课题组的研究成果提出将缓中补虚、活血化瘀功效与寒凉药性结合,利用现代新型科学技术,结合中医理论进行整体与拆方研究,为大黄(庶)虫丸抗肿瘤的研究提供新思路.

Fisetin, a natural flavonoid found in a variety of edible and medical plants, has been suggested to inhibit the proliferation of various tumor cells and to induce apoptosis. However, the effects of fisetin on breast cancer have rarely been reported and the underlying mechanism is still undefined. The present study explored the anti‑cancer effects of fisetin on mammary carcinoma cells and the underlying mechanisms. Following treatment with fisetin, viability of 4T1, MCF‑7 and MDA‑MB‑231 cells were measured by MTT assay. The inhibitory effects of fisetin on proliferation, migration and invasion were evaluated in 4T1 cells using proliferation array, wound‑healing assay, and HUV‑EC‑C‑cell barrier based on electrical cell‑substrate impedance sensing platform. Cell apoptosis was analyzed by flow cytometry, and western blotting analysis was performed to identify target molecules. A 4T1 orthotopic mammary tumor model was used to assess the fisetin‑inhibition on tumor growth in vivo. Test kits were used to examine the liver and kidney function of tumor‑bearing mice. The results suggest that fisetin suppressed the proliferation of breast cancer cells, suppressed the metastasis and invasiveness of 4T1 cells, and induced the apoptosis of 4T1 cells in vitro. The potent anti‑cancer effect of fisetin was associated with the regulation of the phosphatidylinositol‑3‑kinase/protein kinase B/mammalian target of rapamycin pathway. In vivo experiments demonstrated that fisetin suppressed the growth of 4T1 cell‑derived orthotopic breast tumors and enhanced tumor cell apoptosis, and the evaluated alanine amino transferase and aspartate amino transferase levels in serum of tumor‑bearing mice suggested that fisetin may lead to side effects on liver biochemical function. The present study confirms that fisetin exerted an anti‑mammary carcinoma effect. However, in vivo experiments also revealed that fisetin had low solubility and low bioavailability. Further investigation is required to determine the clinical value of fisetin.

Fisetin, a natural flavonoid found in a variety of edible and medical plants, has been suggested to inhibit the proliferation of various tumor cells and to induce apoptosis. However, the effects of fisetin on breast cancer have rarely been reported and the underlying mechanism is still undefined. The present study explored the anti-cancer effects of fisetin on mammary carcinoma cells and the underlying mechanisms. Following treatment with fisetin, viability of 4T1, MCF-7 and MDA-MB-231 cells were measured by MTT assay. The inhibitory effects of fisetin on proliferation, migration and invasion were evaluated in 4T1 cells using proliferation array, wound-healing assay, and HUV-EC-C-cell barrier based on electrical cell-substrate impedance sensing platform. Cell apoptosis was analyzed by flow cytometry, and western blotting analysis was performed to identify target molecules. A 4T1 orthotopic mammary tumor model was used to assess the fisetin-inhibition on tumor growth in vivo. Test kits were used to examine the liver and kidney function of tumor-bearing mice. The results suggest that fisetin suppressed the proliferation of breast cancer cells, suppressed the metastasis and invasiveness of 4T1 cells, and induced the apoptosis of 4T1 cells in vitro. The potent anti-cancer effect of fisetin was associated with the regulation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway. In vivo experiments demonstrated that fisetin suppressed the growth of 4T1 cell-derived orthotopic breast tumors and enhanced tumor cell apoptosis, and the evaluated alanine amino transferase and aspartate amino transferase levels in serum of tumor-bearing mice suggested that fisetin may lead to side effects on liver biochemical function. The present study confirms that fisetin exerted an anti-mammary carcinoma effect. However, in vivo experiments also revealed that fisetin had low solubility and low bioavailability. Further investigation is required to determine the clinical value of fisetin.