Song Shuichuan, Du Leiwen, Jiang Hao, Zhu Xinhai, Li Jinhui, Xu Ji
Department of Gastroenterology, 117 Hospital of People's Liberation Army, Hangzhou, Zhejiang, China (mainland).
Department of Oncology, Zhejiang Hospital, Hangzhou, Zhejiang, China (mainland).
Med Sci Monit. 2016 Oct 18;22:3798-3803. doi: 10.12659/msm.898232.
BACKGROUND Dose-related toxicity is the major restriction of cisplatin and cisplatin-combination chemotherapy, and is a challenge for advanced gastric cancer treatment. We explored the possibility of using Paris saponin I as an agent to sensitize gastric cancer cells to cisplatin, and examined the underlying mechanism. MATERIAL AND METHODS Growth inhibition was detected by MTT assay. The cell cycle and apoptosis were detected using flow cytometry and Annexin V/PI staining. The P21waf1/cip1, Bcl-2, Bax, and caspase-3 protein expression were detected using Western blot analysis. RESULTS The results revealed that PSI sensitized gastric cancer cells to cisplatin, with low toxicity. The IC50 value of cisplatin in SGC-7901 cell lines was decreased when combined with PSI. PSI promoted cisplatin-induced G2/M phase arrest and apoptosis in a cisplatin concentration-dependent manner. Bcl-2 protein expression decreased, but Bax, caspase-3, and P21waf1/cip1 protein expression increased with PSI treatment. CONCLUSIONS The underlying mechanism of Paris saponin I may be related to targeting the apoptosis pathway and cell cycle blocking, which suggests that PSI is a potential therapeutic sensitizer for cisplatin in treating gastric cancer.
背景 剂量相关毒性是顺铂及顺铂联合化疗的主要限制因素,也是晚期胃癌治疗面临的一项挑战。我们探究了使用重楼皂苷I使胃癌细胞对顺铂敏感的可能性,并研究了其潜在机制。材料与方法 采用MTT法检测生长抑制情况。使用流式细胞术和膜联蛋白V/碘化丙啶染色检测细胞周期和细胞凋亡。采用蛋白质免疫印迹分析检测P21waf1/cip1、Bcl-2、Bax和半胱天冬酶-3蛋白表达。结果 结果显示,重楼皂苷I可使胃癌细胞对顺铂敏感,且毒性较低。顺铂与重楼皂苷I联合使用时,SGC-7901细胞系中顺铂的IC50值降低。重楼皂苷I以顺铂浓度依赖性方式促进顺铂诱导的G2/M期阻滞和细胞凋亡。重楼皂苷I处理后,Bcl-2蛋白表达降低,但Bax、半胱天冬酶-3和P21waf1/cip1蛋白表达增加。结论 重楼皂苷I的潜在机制可能与靶向凋亡途径和细胞周期阻滞有关,这表明重楼皂苷I是顺铂治疗胃癌的一种潜在治疗增敏剂。