BACKGROUND:Disruptor of telomeric silencing-1-like (DOT1L), a methyltransferase of H3K79, was observed to be amplified and overexpressed in certain malignancies. This work was aimed at investigating the differences in DOT1L expression and its regulatory mechanism in gastric cancer (GC) and healthy samples. METHODS:Immunohistochemistry was used to detect DOT1L levels in 101 cases of GC and marching adjacent normal tissues. DOT1L was inhibited by small interfering RNA (siRNA) and EPZ5676; a targeting drug. The ability of cells to proliferate were checked by cell counting kit-8 (CCK-8) and clone formation assays, with flow cytometry for observing the cell cycle. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot revealed the gene and protein profiles. Finally, the outcome of EPZ5676 administration was checked on a murine model. RESULTS:The expression of DOT1L is significantly increased in gastric malignant tumors that is related to the degree of differentiation, lymph node metastasis and TNM staging. DOT1L serves as an independent marker for the prognosis of overall survival (OS) with high levels implying worse prognosis. In addition, DOT1L regulates cyclin-dependent kinase (CDK) 4 (CDK4) and CDK6 through H3K79me2, which leads to a change in the cell cycle at G1, thereby affecting the proliferation of tumors in vitro and in vivo. CONCLUSIONS:This is a first clinical demonstration of the applicability of DOT1L overexpression in gastric tumors. The work is suggestive of altered proliferation of cells by DOT1L via regulating cyclins and H3K79 methylation. This indicates the role of DOT1L in the prognosis and possible medical intervention of GC.
This study delineates a hierarchical signaling axis driving gastric cancer (GC) progression through integrated transcriptomic and functional analyses. Single-cell sequencing and TCGA data identified CSF2 as a key oncogene, with elevated expression correlating with poor prognosis. Mechanistically, the transcription factor HES1 directly activates IGF2BP2 transcription, as confirmed by chromatin immunoprecipitation and dual-luciferase assays. IGF2BP2 subsequently stabilizes CSF2 mRNA via N6-methyladenosine (m6A) modification, validated through RNA immunoprecipitation and mRNA decay kinetics. Functional interrogation revealed that the HES1-IGF2BP2-CSF2 axis promotes GC cell growth, motility, and infiltrative capacity while inhibiting apoptosis. Critically, this axis orchestrates glycolytic reprogramming, evidenced by upregulated HK2/PKM2/LDHA expression, increased lactate/ATP production, and enhanced glycolytic flux. In vivo xenografts demonstrated accelerated tumor growth upon axis activation, with immunohistochemistry showing elevated Ki67 and reduced apoptosis. These results establish a novel signaling cascade wherein HES1 transcriptionally integrates IGF2BP2-mediated m6A epitranscriptomics and metabolic rewiring to fuel GC aggressiveness.
This study reports the synthesis and characterization of an injectable nano-hydrogel composite (m@NPs-HG) based on selenium nanoparticles (Se NPs) and carboxymethyl chitosan (CMCS) nanoparticles for enhanced cancer therapy. Selenium nanoparticles were stabilized using CMCS to form copper selenide nanoparticles (CSe NPs), while doxorubicin (DOX)-loaded CMCS nanoparticles (CD NPs) were encapsulated within cancer cell membranes to generate biomimetic nanoparticles (m@NPs). Subsequently, CSe NPs and m@NPs were integrated into a hydrogel via crosslinking with CuCl2, resulting in the formation of m@NPs-HG. The composite exhibited remarkable photothermal conversion capability, efficient cellular uptake, and robust reactive oxygen species (ROS) generation. In vitro experiments demonstrated significant induction of apoptosis and cytotoxicity in H22 and HepG2 cancer cells. The in vivo anti-tumor efficacy was evaluated in H22 tumor-bearing mice, revealing that m@NPs-HG combined with laser irradiation effectively suppressed tumor growth while exhibiting minimal systemic toxicity. Hemolysis and biodistribution studies further confirmed the excellent biocompatibility and targeting ability of the composite system. This study concludes that the m@NPs-HG system represents a promising theranostic platform for cancer treatment.
Gastric cancer (GC) is a leading cause of cancer-related deaths globally, necessitating the identification of novel therapeutic targets. This study investigates the roles of MATN3 and ASPN in GC progression via the epithelial-mesenchymal transition (EMT) pathway. Analysis of the Cancer Genome Atlas-Stomach Adenocarcinoma (TCGA-STAD) dataset revealed that both MATN3 and ASPN are significantly upregulated in GC tissues and correlate with poor patient survival. Protein-protein interaction and co-expression analyses confirmed a direct interaction between MATN3 and ASPN, suggesting their synergistic role in EMT activation. Functional assays demonstrated that MATN3 promotes GC cell proliferation, migration, and invasion, while its knockdown inhibits these malignant behaviors and induces apoptosis. ASPN overexpression further amplified these oncogenic effects. In vivo, studies in a mouse model corroborated that co-overexpression of MATN3 and ASPN enhances tumor growth and metastasis. These findings highlight the MATN3-ASPN axis as a potential therapeutic target in GC, offering new insights into the molecular mechanisms driving GC progression.
The purpose of this paper is to develop a pH/thermal sensitive nanohydrogel composite for in situ injection and to achieve an enhanced chemo-photothermal synergistic antitumor effect. Pluronic F127 was oxidized to aldehyde-terminated (AF127) as the precursor of the thermally sensitive hydrogel. A series of hydrogels (HG) with different rheological behaviors were obtained by adjusting the ratio of AF127 to carboxymethyl chitosan (CMCS) (AF45/CM15, AF75/CM15, and AF90/CM15). By changing the ratio of AF127 micelles to CMCS, we can adjust the sol-gel transition time and temperature to facilitate in situ tumor injection. Indocyanine green (ICG) encapsulated AF127 micelles and doxorubicin (DOX)-loaded CMCS nanoparticles (NP-DOX) can form nanohydrogel composite (HG/ICG/NP-DOX) through dynamic Schiff base covalent bonds and physical entanglement. The nanohydrogel composite has good fluidity for injection at low temperatures and can quickly form hydrogel at 37 ?. Bromelain was introduced into the complex to improve the penetration of nanoparticles by hydrolyzing the dense extracellular matrix (ECM) in tumor tissue. ICG can produce a photothermal effect under 808 nm laser irradiation, further enhancing the antitumor effect of NP-DOX. HG/ICG/NP-DOX can remain in the tumor area for a long time, and it still shows an obvious photothermal effect even after 120 h. HG/ICG/NP-DOX with laser irradiation possesses an excellent chemo-photothermal synergistic antitumor effect, and the tumor growth inhibition rate reached 93.9%. These nanohydrogel composites have great potential in the field of in situ tumor injection as local drug delivery systems.
目的:探究奥沙利铂(L-OHP)与吴茱萸碱(EVO)联用后对L-OHP耐药的人胃癌BGC-823/L-OHP细胞增殖与凋亡能力的改变及可能机制.方法:于体外建立对L-OHP耐药的胃癌BGC-823细胞株,CCK-8法分别计算EVO及L-OHP单独使用与联合使用时BGC-823/L-OHP细胞的增殖抑制率、IC50及逆转指数;流式细胞仪检测EVO联合L-OHP作用于BGC-823/L-OHP细胞前后细胞周期分布及凋亡的变化;采用Real-time PCR、Western blot法检测细胞中MDR1、MRP1 mRNA和蛋白的表达水平.结果:2.00 μmol/L EV O处理BGC-823/L-OHP细胞48 h后,L-OHP对BGC-823/L-OHP耐药细胞株的IC,.由(18.83±0.83)μg/ml变为(12.78±1.78)μg/ml,差异有统计学意义(P<0.05);EVO与L-OHP联用耐药细胞滞留在G2期比例升高,滞留在G1期及S期的细胞比例降低(P<0.05);细胞凋亡率高于单独用药组(P<0.05);MDR1、MRP1 mRNA和蛋白表达水平低于单独用药组(P<0.05).结论:EVO和L-OHP联用能逆转BGC-823/L-OHP对L-OHP的耐药性并改变其周期分布,促进细胞凋亡.
To compare the effects of Ivor-Lewis esophagectomy and McKeown esophagectomy on perioperative anxiety and depression in patients with esophageal cancer. Sixty-three patients with stage I-III middle and lower esophageal carcinoma from June 2021 to December 2022 were randomly divided into observation group (n = 32) treated with laparoscopic Ivor-Lewis esophagectomy and control group (n = 31) treated with laparoscopic McKeown esophagectomy. Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) were measured on the second day of admission and the fifth day after surgery to assess the presence of depression and anxiety. The preoperative and postoperative clinical data of both groups were compared, and multivariate analysis was used to identify risk factors associated with depression and anxiety in patients with esophageal cancer. There was no significant difference in SDS and SAS standard scores between the observation group and the control group ( P > 0.05). The postoperative SDS and SAS scores in the control group were significantly higher than those before and after operation in the observation group ( P < 0.01). According to univariate analysis, patients with TNM stage III, tumor diameter greater than 3 cm, postoperative complications, radical McKeown esophagectomy, and C-reactive protein levels above 10 mg/L had a higher incidence of depression and anxiety ( P < 0.05). Multivariate logistic analysis showed that TNM stage III (depression: OR 1.683, 95 CI 1.429–1.861; Anxiety: OR 1.739, 95 CI 1.516–1.902), postoperative complications (depression: OR 2.345, 95 CI 1.435–3.891; Anxiety: OR 1.872, 95 CI 1.372–3.471), surgical approach (depression: OR 1.609, 95 CI 1.502–3.193; Anxiety: OR 1.658, 95 CI 1.469–2.059), and C-reactive protein (depression: OR 2.260, 95 CI 1.157–4.059; Anxiety: OR 0.373, 95 CI 0.253–0.976) were all independent factors for depression and anxiety in patients after esophageal cancer surgery ( P < 0.05). The Ivor-Lewis esophagectomy has the advantages of fewer complications and low inflammatory response, which can help alleviate anxiety and depression and improve patients’ quality of life and prognosis.
Background and Aims: In radical gastrectomy for proximal gastric cancer, bleeding and spleen damage are likely to occur when dealing with short gastric vessels, especially in some obese patients with short spleen-gastric ligaments at the upper pole of the spleen. The author’s team has previously used a surgical method of pre-expanding the posterior gastric space, which effectively solves this problem. This study was performed to compare the clinical efficacy of laparoscopic proximal gastrectomy with pre-expansion of the retrogastric space versus conventional laparoscopic proximal gastrectomy, and explore the value of the pre-expansion method in laparoscopic proximal gastrectomy for gastric cancer.Methods: The clinical data of 196 patients who underwent laparoscopic proximal radical gastrectomy in the Department of Oncology of the First Affiliated Hospital of Bengbu Medical College from January 2019 to December 2021 were retrospectively analyzed. Of the patients, 99 cases underwent radical proximal gastrectomy with pre-expansion of the retrogastric space(study group), 97 cases received conventional proximal gastrectomy(control group). The clinical variables were compared between the two groups of patients.Results: There were no significant differences in general information such as age, sex, BMI, tumor location, tumor stage, surgical method, and esophagojejunostomy method between the two groups(all P>0.05). All patients in both groups completed the laparoscopic surgery uneventfully, with the same range of lymph node dissection and without conversion to open surgery. Compared with the control group, the study group had a significantly shorter average operative time [(100.3±25.8) min vs.(130.7±43.2) min, P=0.000] and significantly less average intraoperative blood loss [(35.0±5.7) mL vs.(44.9±4.7) mL, P=0.000]. Splenic injury occurred in 5 cases(5.2%) in the control group during the surgery, while no intraoperative spleen injury occurred in the study group, but the difference was not statistically significant(P>0.05). There were no statistically significant differences between the two groups in terms of the number of lymph node dissection, postoperative drainage volume, drainage time, postoperative hospital stay, hospital costs, and incidence of surgical complications(all P>0.05). No serious postoperative complications occurred in both groups of patients.Conclusion: The surgical method of pre-expanding the posterior gastric space in laparoscopic proximal gastrectomy has the advantages of less intraoperative bleeding, shorter operation time, and reduced iatrogenic splenic injury. So, it is recommended for clinical use.
Abstract Purpose To analyze the clinical efficacy of total laparoscopic π-shaped esophageal jejunostomy and laparoscopic assisted Roux en-Y esophago-jejunostomy for cardiac cancer and their effects on traumatic stress. Methods We collected clinical data from 72 patients with adenocarcinoma of the esophagogastric junction who were treated in our department between June 2020 and July 2022. All patients underwent laparoscopic total gastrectomy + D2 lymphadenectomy, in whom 38 patients underwent total laparoscopic total gastrectomy with π-shaped esophageal jejunostomy and 34 patients underwent laparoscopic-assisted total gastrectomy with Roux en-Y esophago-jejunostomy. The short-term therapeutic effects, safety and effects on stress response indicators of different surgical methods were analyzed. Results There were no significant differences in baseline clinical and pathological data between the two groups (P > 0.05). The mean operation duration was 201.7 ± 80.3 minutes in the total endoscopic π-shaped esophageal jejunostomy group, which was longer than 166.9 ± 26.9 minutes in the laparoscopic-assisted Roux en-Y esophago-jejunostomy group (P < 0.05). The length of the surgical incision in the total endoscopic π-shaped esophageal jejunostomy group was significantly shorter, measuring 4.6 ± 2.1 cm, compared to the Roux-en-Y anastomosis group, which had an average length of 10.4 ± 2.1 cm (P < 0.01). In terms of intraoperative bleeding, the intraoperative bleeding volume of 130.3 ± 50.3 ml in the total endoscopic π-shaped esophageal jejunostomy group was significantly lower than that of 167.2 ± 72.8 ml in the laparoscopic-assisted Roux en-Y esophago-jejunostomy group (P < 0.05). Postoperative recovery time to exhaust was 3.8 ± 1.2 days in total endoscopic π-shaped esophageal jejunostomy group, significantly lower than 5.0 ± 2.0 days in laparoscopic-assisted Roux en-Y esophago-jejunostomy group (P = 0.003). In terms of postoperative extubation time, postoperative hospital stay, postoperative complications and the number of dissected lymph nodes, there were no significant differences between the total endoscopic π-shaped esophageal jejunostomy group and the laparoscopic-assisted Roux en-Y esophago-jejunostomy group (P > 0.05). In terms of stress indicators, there were no significant differences in stress indicators between the two groups before surgery, and the serum levels of CRP, cortisol (COR) and IL-6 in the π anastomosis group were significantly lower than those in the Roux en-Y esophago-jejunostomy group on postoperative days 3 and 5 (P < 0.05). Conclusion Total laparoscopic total gastrectomy with π-shaped esophageal jejunostomy demonstrates safety and feasibility. This surgical approach effectively reduces intraoperative bleeding, accelerates patient recovery time, minimizes postoperative pain, lowers the risk of complications, and minimally impacts the body's traumatic stress response.
目的:探究基于成果导向的教学模式在肿瘤外科学教学中的应用.方法:将2021年1月至2022年1月在蚌埠医学院第一附属医院学习的120名临床见习学生,随机分为对照组和观察组,每组60名.对照组采用常规授课方式进行教学,观察组采用基于成果导向的教学模式.对2组学生的成绩以及对教学的满意度进行分析.结果:观察组学生的理论成绩及实践成绩均高于对照组(P<0.01);观察组学生对课程效果、知识收获和实践的满意度均高于对照组学生(P<0.01).结论:基于成果导向的教学模式应用在肿瘤外科学临床见习学生的教学工作中,能够提高教学质量,提升学生满意度,使学生更主动地获取知识和提高成绩,值得进一步探究和推广.
Abstract Background: The aim of this study was to investigate the co-operative role of CXCR4/ CXCL12 axis and IL-1Ra in metastatic processes mechanism by interactions between colorectal cancer cells and stromal cells in their microenvironment. Methods: Expression of IL-1a, CXCL12 and CXCR4 mRNA and proteins were determined by RT-PCR and Western blot. The effect of secreted level of CXCL12 by IL-1Ra on fibroblasts was measured by ELISA. CXCL12 regulate metastatic potential of colorectal cancer was evaluated by proliferation, invasion and angiogenesis assays, respectively, in which invasion and angiogenesis assays used an in vitro system consisting of co-cultured colorectal cells and stromal cells. Results: IL-1a was expressed in high liver metastatic colorectal cancer cell lines (HT-29 and WiDr). The colorectal cancer cell-derived IL-1a and rIL-1a significantly promoted CXCL12 expression by fibroblasts, and this enhancing effect can be significantly inhibited by IL-1Ra (P<0.01). CXCL12 not only enhanced the migration and proliferation of human umbilical vein endothelial cells (HUVECs), but also significantly enhanced angiogenesis (P<0.01). Furthermore, the high liver-metastatic colorectal cancer cell line (HT-29), which secretes IL-1a, significantly enhanced angiogenesis compared to the low liver-metastatic cell line (CaCo-2), which does not produce IL-1a (P<0.01). On the contrary, IL-1Ra can significantly inhibit migration, proliferation and angiogenesis (P<0.01). Conclusion: Autocrine IL-1a and paracrine CXCL12 co-enhances the metastatic potential of colorectal cancer cells; IL-1Ra can inhibit the metastatic potential of colorectal cancer cells via decrease IL-1a/CXCR4/CXCL12 signaling pathways.
目的:探讨胃癌病人全胃切除术后早期经口肠内营养的安全性与可行性.方法:选择行腹腔镜辅助根治性全胃切除术的胃癌病人,依照肠内营养方式不同分为早期经口营养(无营养管组,25例)和经空肠营养管肠内营养(有营养管组,23例).分析比较2组病人术后并发症发生情况、术后应激反应指标、术后营养指标、术后肠道屏障功能指标、术后排气时间及术后住院时间.结果:2组病人在术后营养指标、术后排气时间及住院时间方面差异均无统计学意义,在术后咽喉疼痛、腹泻发生率方面,无营养管组明显优于有营养管组(P<0.01和P<0.05),且术后C反应蛋白水平、血D-乳酸和I-FABP水平,无营养管组均低于有营养管组(P<0.05~P<0.01).结论:对于全胃切除的胃癌病人,与经鼻空肠营养管肠内营养相比,早期经口营养是安全的,并能减少病人咽部不适、腹泻的发生率,减轻机体应激反应,促进机体肠道屏障功能修复.
目的 探究糖酵解抑制剂WZB117通过下调Yes相关蛋白(YAP)影响病人来源的胃癌细胞干性和糖酵解的机制.方法 胰蛋白酶消化临床获取的胃癌组织,培养制备胃癌细胞;细胞分为正常组、低糖对照组和WZB117处理组,qRT-PCR检测细胞干性相关基因(Nanog、oct-4、sox-2)、基质金属蛋白酶-2 (MMP-2)、基质金属蛋白酶-9(MMP-9)和凋亡相关基因(Bcl-2、bax和Cyt-C)的表达;Western blot测定细胞中YAP和代谢相关蛋白己糖激酶2(HK2)、丙酮酸激酶M2亚型(PKM2)和活化的含半胱氨酸的天冬氨酸蛋白水解酶3(Cleaved Caspase-3)的表达;MTT测定细胞增殖活性;平板克隆实验测定细胞克隆形成能力;划痕试验观察细胞迁移能力;Transwell实验观察细胞的侵袭能力;试剂盒测定细胞中三磷酸腺苷(ATP)及培养液上清液中的乳酸含量.结果 WZB117培养细胞后,YAP表达水平较正常组及低糖对照组显著降低(P<0.05);Nanog、BMil、c-Myc的表达以及细胞增殖活性、克隆形成率、侵袭能力、迁移能力降低(P<0.05);Cleaved Caspase-3水平及细胞凋亡率升高(P<0.05);Bcl-2表达随WZB117浓度增高而降低(P<0.05);Bax和Cyt-C表达随WZB117浓度增高而升高(P<0.05);ATP、上清液中乳酸含量以及HK2、PKM2蛋白水平降低(P<0.05).结论 抑制剂WZB117可通过下调胃癌细胞中YAP表达,干扰糖酵解关键酶HK2、PKM2的表达,抑制胃癌细胞糖酵解,降低细胞ATP水平.
Background: Gastric cancer (GC) is a common malignancy with high morbidity. Long non-coding RNAs (LncRNAs) have been demonstrated to be critical post-transcriptional regulators in tumorigenesis. This study aimed to investigate the effect of LncRNA NEAT1 on the proliferation and metastasis of GC. Material and Methods: The expression of LncRNA NEAT1 was examined in clinical samples and GC cell lines. GC cell lines (SGC-7901 and BGC-823) and human normal gastric epithelial cell line (GES-1) were employed. The correlation between NEAT1, miR-103a and STAMBPL1 was determined by luciferase reporter assay. Cell viability was determined by CCK8 assay. Cell invasion capacity was examined by Transwell assay. The protein level of STAMBPL1 was analyzed by western blotting. Results: LncRNA NEAT1 was found to be up-regulated in GC cell lines. Further studies identified LncRNA NEAT1 as a direct target of miR-103a. Moreover, NEAT1 knockdown and miR-103a overexpression inhibited cell proliferation and cell invasion. NEAT1 knockdown and miR-103a overexpression also decreased STAMBPL1 levels. Conclusion: Our study indicated that LncRNA NEAT1 was up-regulated in GC cells and tissues. NEAT1 was targeted and inhibited by miR-103a and acted as an oncogene, which promoted the malignant behavior of GC cells. This regulatory effect of NEAT1 may be associated with STAMBPL1. Therefore, NEAT1 could be used as a biomarker for predicting the progression of GC.
目的 探讨长链非编码RNA NEAT1(lncRNA NEAT1)在胃癌组织和细胞中的表达,以及其通过调控miR-103a/STAMBPL1轴对胃癌细胞增殖和侵袭的影响.方法 采用qRT-PCR法检测胃癌组织及癌旁组织中lncRNA NEAT1的表达水平;采用qRT-PCR法检测人正常胃上皮GES-1细胞及胃癌细胞SGC-7901和BGC-823中lncRNA NEAT1的表达水平.胃癌细胞SGC-7901和BGC-823中分别转染si-NEAT1(si-NEAT1组)和si-NC(si-NC组).采用CCK-8法和Transwell检测细胞增殖和侵袭;采用qRT-PCR和Western blot法分别测定胃癌细胞中miR-103a mRNA和STAMBPL1蛋白的表达变化.结果 与癌旁正常组织或正常细胞GES-1相比,lncRNA NEAT1在胃癌组织及胃癌SGC-7901和BGC-823细胞中表达水平明显增加(P<0.05).与si-NC组相比,si-NEAT1组中胃癌SGC-7901和BGC-823细胞增殖和侵袭能力明显减少(P<0.05),miR-103a mRNA水平增高以及STAMBPL1蛋白表达水平降低(P<0.05).结论 lncRNA NEAT1在胃癌中可能通过调控miR-103a/STAMBPL1信号途径改变胃癌细胞增殖及侵袭的能力.
目的 研究胃癌组织中类端粒沉默干扰体1(disruptor of telomeric silencing 1-like,DOTIL)基因的表达情况及其与临床病理学因素和预后之间的相关性.方法 收集25例胃癌及其对应的癌旁正常新鲜组织,通过qRT-PCR和Western Blot检测DOT1L mRNA和蛋白的表达水平.应用免疫组化方法检测80例胃癌组织和与其配对的癌旁正常组织蜡块中DOT1L蛋白的表达情况,分析DOT1L蛋白表达与胃癌临床病理参数之间的关系及其对患者预后的影响.结果 与癌旁正常组织相比,在胃癌组织中的DOT1L mRNA和蛋白表达水平明显升高.DOT1L蛋白的表达水平与分化程度、TNM分期、淋巴转移有关,并且DOT1L是胃癌总体生存期的独立预后因素,DOT1L表达越高,患者预后越差.结论 胃癌中DOT1L的表达量明显升高,阳性表达提示预后不良.这些提示DOT1L可能是胃癌预测预后以及治疗干预的潜在靶点.
目的:探讨三阴性乳腺癌(TNBC)的上皮间质转化(EMT)及自噬特性的差异.方法:选取TNBC细胞株BT-549与非TNBC细胞株MCF-7,分别对比其EMT及自噬特性.通过细胞形态,平板克隆,Transwell侵袭实验,Western blotting实验测定其EMT的差异,通过电镜观察自噬体,免疫荧光实验,Western blotting实验测定其自噬特性.结果:TNBC增殖性和侵袭性强于非TNBC,TNBC组间质细胞标志物N-cadherin、Vimentin、β-catenin相对高表达,非TNBC组上皮细胞标志物E-cadherin相对高表达.电镜下,非TNBC细胞线粒体自噬,TNBC组自噬微管相关蛋白1轻链3相对高表达.结论:TNBC增殖性、侵袭性皆强于非TNBC,EMT及自噬化程度均较高.
目的 观察抑制DOT1L基因表达对胃癌MGC-803细胞增殖、迁移及侵袭的影响,并探讨其机制.方法 采用Western blot检测BGC-823、MGC-803、SGC-7901胃癌细胞系中DOT1L基因的表达量;分别采用Real-time PCR、Western blot检测各组细胞DOT1L mRNA和相关蛋白表达量;通过细胞集落克隆实验和CCK-8法检测细胞增殖能力;通过Tran-swell实验和划痕损伤实验检测细胞侵袭和迁移能力;通过Western blot检测细胞中的上皮间质转化(EMT)相关分子(E-Cadherin、N-Cadherin、Vimentin)的蛋白表达量.结果 DOT1L在3种胃癌细胞中呈不同程度表达,在MGC-803细胞中表达量最高;转染后DOT1L相关蛋白及mRNA的表达能力显著降低(P<0.05);与对照组比较,细胞增殖、侵袭和迁移能力均明显减弱(P<0.05);细胞中N-Cadherin、Vimen-tin蛋白表达减少(P<0.05),E-Cadherin蛋白表达增加(P<0.05).结论 抑制DOT1L基因表达可降低胃癌MGC-803细胞的增殖与集落形成能力;并通过调控N-Cadherin、Vim-entin,E-Cadherin的表达逆转EMT进程,进而减弱胃癌MGC-803细胞的迁移和侵袭能力.