SP-141抑制胃癌细胞增殖、迁移并促进凋亡

SP-141 inhibits cell proliferation, migration, and promotes apoptosis in gastric cancer cells

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。

Objective： To investigate the effects of MDM2 inhibitor SP-141 on proliferation, apoptosis and migration in MGC803 and BGC823 human gastric cancer cells. Methods： The cell viability, proliferation, cell cycle distribution, apoptosis and migration were detected by CCK-8 method, colony formation assay, flow cytometry analysis, Hoechst staining assay and wound-healing assay, respectively. Western Blot was performed to determine the levels of MDM2 and relative biomarkers in SP-141 treated MGC803 and BGC823 cells. Results： The m RNA expressions of MDM2 was significantly increased in gastric cancer tissues compared with adjacent non-cancerous tissues（P〈0.01） in TCGA gastric cancer database. MDM2 expressions did not show obvious differences among five different human gastric cancer cell lines. SP-141 inhibited the cell viability and colony numbers in MGC803 and BGC823, and induced cell cycle arrest at G2/M phase. SP-141 induced cellular apoptosis with down-regulating Bcl-2 as well as up-regulating Bax,cleaved-Caspose-3 and cleaved-PARP1 expressions. SP-141 also suppressed the wound closure in MGC803 cells, and accompanied by the decreased FAK protein expression. Conclusion： The MDM2 specific inhibitor SP-141 effectively suppresses cell proliferation,migration, and promotes apoptosis in human gastric cancer cells.