[关键词]
[摘要]
目的:探究组蛋白甲基转移酶G9a 在胃癌组织中的表达及其与预后的相关性,并观察G9a 抑制剂对胃癌细胞增殖和凋亡的影响。方法:通过Kaplan-Meier Plotter 和Oncomine 数据库分析G9a 在胃癌组织中的表达水平及其与预后的相关性。选用人胃癌细胞株SGC-7901 和MKN-45 为研究对象,Western blotting 方法检测细胞中G9a 蛋白表达水平,以G9a 抑制剂BIX01294处理胃癌细胞,观察细胞形态变化,CCK-8 法和集落形成实验检测胃癌细胞增殖能力和集落形成率的变化,流式细胞术检测细胞凋亡的变化。结果:G9a 在胃癌组织中高表达(P<0.01),其高表达与预后不良呈正相关(P<0.01)。BIX01294 能使胃癌细胞体积缩小、细胞间连接消失,甚至细胞皱缩、变圆、脱落等。BIX01294 能显著抑制胃癌细胞集落形成和胃癌细胞的增殖(均P<0.05),同时促进胃癌细胞凋亡(P<0.05)。结论: G9a 在胃癌组织中高表达,其高水平表达与预后不良呈正相关;抑制G9a 的表达可显著抑制胃癌细胞的增殖和促进细胞凋亡。
[Key word]
[Abstract]
Objective: To investigate the expression of histone methyltransferase G9a in gastric cancer tissues and its correlation to prognosis, and to observe the effect of G9a inhibitor on the proliferation and apoptosis of gastric cancer cells. Methods: The expression level of G9a in gastric cancer tissues and its correlation to prognosis were analyzed by using the Kaplan-Meier Plotter and Oncomine database. Human gastric cancer cell line SGC-7901 and MKN-45 were selected as study subject. The expression level of G9a protein was detected by Western blotting. The morphological change of gastric cancer cells after the treatment of G9a inhibitor BIX01294 was observed. CCK-8 proliferation experiment and plate colony formation assay were used to examine the proliferation ability and clone formation rate of gastric cancer cells. The changes of cell apoptosis were detected by Annexin-V staining. Results: G9a was highly expressed in gastric cancer tissues (P<0.01), and the high expression of G9a was positively correlated with poor prognosis of gastric can-cer patients (P<0.01). After the treatment of BIX01294, the morphology of gastric cancer cells was changed, the volume of gastric cancer cells reduced, the intercellular connections disappeared, and even the apoptotic manifestations appeared, such as the shrinking,, becoming round and cast-off etc. BIX01294 could significantly inhibit the proliferation and colony formation but promote the apoptosis of gastric cancer cells (all P<0.05). Conclusion: Histone methyltransferase G9a was highly expressed in gastric cancer tissues, and its high expression level was positively correlated with poor prognosis. The proliferation of gastric cancer cells was obviously inhibited while the apoptosis was significantly promoted after inhibiting G9a expression.
[中图分类号]
[基金项目]
国家自然科学基金资助项目(No. 81424003);西安市科技计划项目资助[No. 2017113SF/YX007(7)];肿瘤生物学国家重点实验室(空军军医大学)开放基金研究项目(No. CKSKL201726)