雷帕霉素在顺铂诱导HeLa细胞凋亡中的协同作用  

Synergistic augmentation of cisplatin-induced apoptosis in HeLa cells by rapamycin

作　　者：刘勇[1] 方勇[1] 汪辉[1] 马丁[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院妇产科,武汉430030

出　　处：《华中医学杂志》2009年第6期300-303,共4页Central China Medical Journal

基　　金：国家973重点基础研究发展计划资助项目(2002CB513107);青年科学基金资助项目(No.30600668);国家自然科学基金海外或港;澳青年学者合作研究基金项目(No.30628029)

摘　　要：目的评价雷帕霉素联合顺铂对宫颈癌HeLa细胞的协同作用。方法HeLa细胞经雷帕霉素和(或)顺铂处理后,以MTT法检测细胞的增殖情况。以流式细胞仪检测细胞凋亡。Western blot检测p-4E-BP1和p-S6K1的表达情况。结果雷帕霉素联合顺铂抑制HeLa细胞的增殖,且随时间延长抑制作用越显著,与单独用药组相比差异有显著性。雷帕霉素可增强顺铂诱导的HeLa细胞凋亡。经雷帕霉素作用后的HeLa细胞表达p-4E-BP1和p-S6K1较对照组下降,两者联用明显下降。结论雷帕霉素和顺铂联用在抑制HeLa细胞增殖并诱导其凋亡上具有协同作用。这预示着雷帕霉素和顺铂联用可能是一种合理的靶向治疗宫颈癌的方法。Objective To evaluate the synergistic effect of rapamycin and cisplatin in cervical cancer cell line HeLa. Methods By using HeLa cells, cell proliferation was assessed by MTT assay after exposure to rapamycin, cisplatin, or both in combination. Apoptosis was analyzed by flow cytometry, Immunoblot analysis was performed to detect the expression of phos-phorylated 4E-BP1 and S6 kinase 1. Results Rapamycin and cisplatin inhibited growth of HeLa cells in a time-dependent manner. Simultaneous exposure of cisplatin in combination with rapamycin resulted in a significantly synergistic antiproliferative effect. Rapamycin increased cisplatin-induced apoptosis in HeLa cells. Rapamycin inhibited the expression of phosphorylated 4E-BP1 and S6 kinase 1 in HeLa cells, and combined treatment with cisplatin inhibited the expression over that of rapamycin a-lone. Conclusion The results of the current study provide evidence of a synergistic relation between rapamycin and cisplatin in both inhibition of HeLa cells growth and induction of apoptosis. This suggests that rapamycin and cisplatin may be a rational combination of a targeted therapy for cervical cancer.

关 键 词：雷帕霉素 顺铂 HELA细胞 凋亡 

分 类 号：R737.33[医药卫生—肿瘤]