Niu Peiguang, Shi Daohua, Zhang Shusheng, Zhu Yanting, Zhou Jintuo
Department of Pharmacy, Fujian Provincial Maternity and Children Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350001, P.R. China.
Oncol Lett. 2018 Mar;15(3):3991-3997. doi: 10.3892/ol.2018.7743. Epub 2018 Jan 8.
The mammalian target of rapamycin (mTOR) is well-known as a promising therapeutic target in various cancer cells. mTOR activation decreases the sensitivity of ovarian cancer to cisplatin. Cardamonin inhibits the proliferation of various cancer cells by mTOR suppression. The present study examined whether cardamonin combined with cisplatin is efficacious for the anti-proliferation of ovarian cancer cells. The anti-proliferative effect was determined by MTT and cell cycle assays. Activation of the mTOR signal pathway and the expression of anti-apoptotic proteins were evaluated by western blot analysis. Cardamonin significantly enhanced the effects of cisplatin on cell proliferation and cell cycle progression. The expression of B cell lymphoma-2, X-linked inhibitor of apoptosis protein and Survivin was significantly decreased following combination treatment. Furthermore, the activation of mTOR and its downstream 70 kDa ribosomal protein S6 kinase was inhibited by cardamonin. These results demonstrated that the combinatorial effects of cardamonin and cisplatin on anti-proliferation were enhanced by suppressing the expression of anti-apoptotic proteins and activation of mTOR in ovarian cancer cells.
雷帕霉素哺乳动物靶点(mTOR)作为各种癌细胞中一个有前景的治疗靶点而广为人知。mTOR激活会降低卵巢癌对顺铂的敏感性。小豆蔻明通过抑制mTOR来抑制各种癌细胞的增殖。本研究检测了小豆蔻明联合顺铂对卵巢癌细胞增殖的抑制作用是否有效。通过MTT法和细胞周期分析来确定抗增殖作用。通过蛋白质免疫印迹分析评估mTOR信号通路的激活和抗凋亡蛋白的表达。小豆蔻明显著增强了顺铂对细胞增殖和细胞周期进程的作用。联合治疗后,B细胞淋巴瘤-2、凋亡蛋白X连锁抑制因子和生存素的表达显著降低。此外,小豆蔻明抑制了mTOR及其下游70 kDa核糖体蛋白S6激酶的激活。这些结果表明,小豆蔻明和顺铂通过抑制卵巢癌细胞中抗凋亡蛋白的表达和mTOR的激活,增强了联合抗增殖作用。