二甲双胍和紫杉醇对卵巢癌SKOV3细胞体外增殖和凋亡的影响

目的：研究二甲双胍联合紫杉醇在体外对人卵巢癌SKOV3细胞增殖和凋亡的影响，阐明二甲双胍与紫杉醇的药物协同效应。方法：将卵巢癌SKOV3细胞分为空白对照组、不同浓度（0.01、0.50、1.00、5.00和10.00 mmol·L^-1）二甲双胍组和联合用药组（不同浓度二甲双胍及紫杉醇联合用药）。MTT法检测各组SKOV3细胞增殖抑制率；流式细胞术检测各组SKOV3细胞凋亡率及细胞周期变化；MTT法检测各组SKOV3细胞增殖抑制率。结果：MTT法检测，不同浓度二甲双胍组SKOV3细胞增殖抑制率明显升高，并呈浓度和时间依赖性，与空白对照组比较差异有统计学意义（P<0.05）。流式细胞术检测，不同浓度二甲双胍作用下SKOV3细胞凋亡率明显升高，与空白对照组比较，随着二甲双胍浓度的增加，药物作用48h后实验组SKOV3的细胞凋亡率明显升高（P<0.05）；同时细胞周期发生明显变化，随着二甲双胍浓度的增加，G₀/G₁期细胞百分率降低（P<0.05），而 G₂/M期细胞百分率升高（P<0.05）。MTT法检测，1.00 mmol·L^-1二甲双胍与紫杉醇联合用药组SKOV3细胞增殖抑制率高于0.50 mmol·L^-1二甲双胍与紫杉醇联合用药组（P<0.05）；二甲双胍与紫杉醇联合用药组SKOV3细胞增殖抑制率高于单独紫杉醇组（P<0.05）。结论：二甲双胍通过诱导细胞凋亡抑制卵巢癌细胞SKOV3细胞增殖，二甲双胍能够增强紫杉醇对卵巢癌SKOV3细胞增殖抑制作用，二者具有药物协同效应。

Influence of metformin and paclitaxel in proliferation and apoptosis of ovarian cancer SKOV3 cells in vitro

Objective:To study the influence of metformin and paclitaxel in the proliferation and apoptosis of human ovarian cancer SKOV3 cells in vitro, and to clarify the synergistic effect of metformin and paclitaxel. Methods:The ovarian cancer SKOV3 cells were divided into blank control group, different concentrations (0.01, 0.50, 1.00, 5.00, 10.00mmol·L-1) of metformin groups and combined treatment groups(metformin combined with paclitaxel with different concentrations).The inhibitory rates of proliferation of SKOV3 cells after treated with different concentrations of metformin were detected by MTT method.The apoptotic rates of SKOV3 cells after treated with different concentrations of metformin were measured by flow cytometry.The inhibitory rates of proliferation of SKOV3 cells after treated with metformin and paclitaxel were determined by MTT method.Results:The MTT results showed that the inhibitory rates of proliferation of SKOV3 cells in different concentrations of metformin groups were increased in concentration-and timedependent manner;there were significant differences compared with blank control group (P<0.05).The flow cytometry results showed that the apoptotic rates of SKOV3 cells in different concentrations of metformin groups were increased;compared with control group, with the increasing of concentrations of metformin, the apoptotic rates of SKOV3 cells in experimental groups 48 h after treatment were increased significantly (P<0.05);the percentages of SKOV3 cells in G0/G1 phase were decreased with the increasing of metformin concentrations(P<0.05) and the percentages of SKOV3 cells in G2/M phase were increased(P<0.05).The MTT results showed that the inhibitory rate of proliferation of SKOV3 cells in 1.00 mmol·L-1 metformin+paclitaxel group was higher than that in 0.50 mmol·L-1 metformin+paclitaxel group was higher than that in 0.50 mmol·L-1 metformin+paclitaxel group(P<0.05),and the inhibitory rates of proliferation of SKOV3 cells in combined treatment groups were higher than those in paclitaxel alone groups(P<0.05).Conclusion:Metformin inhibits the proliferation of ovarian cancer SKOV3 cells through the induction of apoptosis.Metformin can enhance the cell proliferation inhibition of paclitaxel on ovarian cancer SKOV3 cells.The combination of metformin and paclitaxel has a synergistic reaction on SKOV3 cells.