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目的:探讨MDM2的新型小分子抑制剂SP-141对胃癌细胞株MGC803和BGC823增殖、凋亡以及迁移的影响。方法:胃癌细胞经SP-141处理后,采用CCK-8法、克隆形成实验、流式细胞术、Hoechst染色法和划痕实验分别检测细胞存活率、细胞增殖、周期分布、凋亡以及迁移能力改变。Western blot检测相关分子蛋白质表达水平。结果:TCGA数据库中32对胃癌组织中的MDM2 m RNA表达水平高于癌旁组织(P<0.01);5种胃癌细胞株均检出MDM2,表达水平差异不大;SP-141抑制MGC803和BGC823的细胞存活率以及克隆形成,诱导其细胞周期阻滞在G2/M期;SP-141增加细胞凋亡发生率,并下调Bcl-2同时上调Bax、Caspase-3剪切体、PARP剪切体的蛋白表达;SP-141抑制细胞迁移并伴有FAK蛋白表达量的下降。结论 :MDM2的新型小分子抑制剂SP-141可有效抑制胃癌细胞增殖、迁移并促进细胞凋亡。
AIM: To investigate the effects of MDM2, a novel small molecule inhibitor SP-141 on proliferation, apoptosis and migration of gastric cancer cell lines MGC803 and BGC823. Methods: The gastric cancer cells were treated with SP-141, and the cell viability, cell proliferation, cycle distribution, apoptosis and migration ability were detected by CCK-8 assay, colony formation assay, flow cytometry, Hoechst staining and scratch assay change. Western blot detection of related protein expression levels. Results: MDM2 m RNA expression in 32 pairs of gastric cancer tissues was higher in TCGA than that in paracancerous tissues (P <0.01). MDM2 was detected in all 5 gastric cancer cell lines with little difference. SP-141 inhibited the expression of MDC2 mRNA in MGC803 and BGC823 The cell cycle arrest in G2 / M phase was induced by SP-141; the apoptosis rate was increased by SP-141, Bcl-2 was down-regulated and Bax, Caspase-3 splicing and PARP splicing SP-141 inhibited cell migration accompanied by decreased FAK protein expression. Conclusion: MDM2, a novel small molecule inhibitor SP-141, can effectively inhibit gastric cancer cell proliferation, migration and promote apoptosis.