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Rapamycin增强上皮性卵巢癌细胞株对顺铂的敏感性研究

Enhanced effects of rapamycin on cisplatin-based chemotherapy in epithelial ovarian cancer cells
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摘要 目的比较单独mTOR抑制剂Rapamycin、单独顺铂或联合2种制剂对上皮性卵巢癌SKOV3、ES-2细胞增殖和凋亡的影响。方法采用Westernblot检测Rapamycin对mTOR的抑制效应,检测顺铂对mTOR信号通路的影响度。采用单独Rapamycin、单独顺铂或联合2种制剂作用于上皮性卵巢癌SKOV3和ES-2细胞,运用MTT和FCM比较不同治疗方案对其增殖和凋亡的影响。结果在正常培养条件下,100nmol/LRapamycin作用24h,上皮性卵巢癌细胞内p-mTOR表达显著抑制;顺铂可影响上皮性卵巢癌ES-2细胞mTOR信号通路的激活情况;与单独顺铂作用和单独Rapamycin作用比较,联合两种制剂显著增加SKOV3和ES-2细胞的早期凋亡率,抑制细胞增殖(P均<0.05)。结论mTOR信号通路在上皮性卵巢癌顺铂化疗中发挥调节作用,Rapamycin可通过抑制mTOR激活而增强顺铂的杀伤作用。 Objective To explore the effects of rapamycin or rapamycin combined with cisplatin on cell proliferation and apoptosis in SKOV3 and ES-2 cells. Methods Western blot was used to detect the inhibiting effect of rapamycin on m TOR and the optical concerntration of rapamycin in SKOV3 and ES-2 cells. Methyl thiazolyl tetrazolium and flowcytometry were used to detect the growth rate and early apoptosis rate after cisplatin-based chemotherapy,rapamycin treatment or combination treatment,respectively. Results The activation of m TOR was dramatically inhibited after exposuring to 100 nmol / L rapamycin under normal culture condition( P 0. 05). Cisplatin could affect the activation of m TOR signaling pathway of ES-2 cells in epithelial ovarian cancer. Compared with single use of cisplatin and rapamycin,the combination use of the two agents could significantly enhance the early apoptosis rate of SKOV3 and ES-2 cells,and inhibit the proliferation of them( P 0. 05). Conclusion m TOR signaling pathway could regulate the cisplatin-based chemotherapy in epithelial ovarian cancer,rapamycin could enhance the killing effect of cisplatin by inhibiting the activation of m TOR.
作者 张海燕 孙红
出处 《实用药物与临床》 CAS 2015年第1期5-9,共5页 Practical Pharmacy and Clinical Remedies
基金 国家自然科学基金(81001150) 高等院校教育部博士点基金(20100071120090) 上海科委医学引导项目(10411960800)
关键词 上皮性卵巢癌 MTOR RAPAMYCIN 顺铂 Epithelial ovarian cancer m TOR signaling Rapamycin Cisplatin
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