雷帕霉素联合顺铂对卵巢癌SKOV3细胞株凋亡和周期的影响

目的:探讨雷帕霉素单独及联合顺铂对卵巢癌SKOV3细胞凋亡、周期的影响及可能的分子机制。方法:体外培养卵巢癌SKOV3细胞,流式细胞术检测雷帕霉素单独及联合顺铂对细胞凋亡及周期分布的影响;实时RT-PCR检测对哺乳动物雷帕霉素靶蛋白(mTOR)mRNA表达的影响。结果:雷帕霉素单独作用可抑制细胞生长增殖,引起G1期阻滞,S期及G2-M期细胞明显减少,使得大部分细胞处于有丝分裂间期,进而促进细胞凋亡,呈现明显的时间依从性,72 h效果最明显;联合顺铂凋亡率明显高于单独用药组(P0.01)。实时RT-PCR结果显示,雷帕霉素作用24 h可引起mTOR mRNA表达下调,72 h抑制表达低于24 h(P0.05)。结论:雷帕霉素作用于PI3K/AKT/mTOR信号传导通路的mTOR位点,阻滞细胞周期,诱导细胞凋亡,与传统化疗药顺铂有协同效应,可增强肿瘤细胞对于顺铂的化疗敏感性。

The effect of rapamycin combined with cisplatin on apoptosis and cell cycle distribution of human ovarian cancer SKOV3 cells

Objective：To study the effect of rapamycin alone or combined with cisplatin on apoptosis and cell cycle distribution of human ovarian cancer SKOV3 cells, and elucidate its possible mechanism. Methods ： SKOV3 cells were cultured in vitro, the effect of rapamycin alone or combined with cisplatin on apoptosis and cell cycle distribution were examined by flow cytometry assay. The expression of mammalian target of rapamyein （ mTOR ） mRNA was detected by qRT-PCR. Results ： Rapamycin alone inhibited the growth of SKOV3 cells, and caused cell cycle arresting at G1 phase, decreased cell number at S and G2 phases, then induced apoptosis happening, which reached the highest inhibition rate at 72 h, and the apoptosis of rapamycin combined with cisplatin was higher than in rapamycin alone group, which had statistical significance （ P 〈 0.01 ）. The qRT-PCR results showed that the expression of roTOR mRNA was decreased in SKOV3 cells treated with rapamyein after 24 h, and further decreased at 72 h （ P 〈 0.05 ）. Conclusions ： Rapamycin inhibits roTOR expression in PI3K/AKT/mTOR cell signal pathway, caused the cell cycle arresting at G1 phase and induced apoptosis. The two drugs in combination show synergy effect, and rapamycin can strengthen the tumor cells chemotherapy sensitivity to cisplatin.