褪黑素联合卡铂对卵巢癌SKOV3细胞体外增殖及凋亡的影响

目的: 探讨褪黑素(MLT)、卡铂(CBP)单独及联合应用在体外对人卵巢癌SKOV3细胞增殖和凋亡的影响,阐明MLT和CBP的药物协同作用。 方法: 将体外培养的人卵巢癌SKOV3细胞分为空白对照组、MLT组(1和2 mmol·L^-1)、CBP组(12.5、25.0和50.0mg·L^-1)、联合用药组(不同浓度MLT及CBP联合用药)。应用MTT比色法、流式细胞术(FCM)测定各组SKOV3细胞的增殖抑制率及凋亡情况,并应用逆转录-聚合酶链式反应(RT-PCR)测定各组SKOV3细胞中Bcl-2和Bax基因表达水平。 结果: MTT法检测,联合用药组SKOV3细胞增殖抑制率高于MLT组,且高于 50.0mg·L^-1CBP组,差异有统计学意义(P<0.05), 2 mmol·L^-1MLT联合50mg·L^-1CBP 组效果最佳,增殖抑制率为(70.7±4.2)%;与双倍浓度CBP组比较,联合用药组SKOV3细胞增殖抑制率明显增高(P<0.05)。流式细胞术检测,联合用药组SKOV3细胞凋亡率高于MLT组,且高于50.0mg·L^-1CBP组,差异有统计学意义(P<0.05), 2mmol·L^-1MLT 联合50mg·L^-1CBP组SKOV3细胞凋亡率为(58.9±2.0)%;与双倍浓度CBP组比较,联合用药组SKOV3细胞凋亡率明显增高(P<0.05)。与同浓度CBP组比较,联合用药组SKOV3细胞中Bax基因表达水平明显升高(P<0.05),Bcl-2基因表达水平明显降低(P<0.05)。 结论: MLT可增强CBP在体外对卵巢癌SKOV-3细胞的增殖抑制作用及促凋亡作用,通过增强Bax基因表达及下调Bcl-2基因表达诱导细胞凋亡。

Effect of melatonin combined with carboplatin on proliferation and apoptosis of ovarian cancer SKOV3 cells in vitro

Objective: To study the effects of melatonin(MLT),carboplatin (CBP),and MLT combined with CBP on the proliferation and apoptosis of human ovarian cancer SKOV3 cells,and to clarify the synergistic effect of MLT and CBP.Methods: The ovarian cancer SKOV3 cells were divided into control group,MLT groups (1and 2mmol·L^-1),CBP groups (12.5,25.0 and 50.0mg·L^-1)and combined treatment groups (MLT combined with CBP with different concentrations). The apoptotic rates and inhibitory rates of proliferation of SKOV3 cells were detected with MTT assay and flow cytometry(FMC),and the expressions of Bcl-2 and Bax in ovarian cancer SKOV3 cells were detected by RT-PCR assay.Results:The MTT results showed that the inhibitroy rates of proliferation of SKOV3 cells in combined groups were higher than those in MLT groups and 50.0mg·L^-1 CBP group(P<0.05). 2mmol·L^-1 MLT combined with 50mg·L^-1 CBP obtained the best result,and the inhibitory rate was (70.7±4.2)% which was higher than that in 50.0mg·L^-1 CBP group (P<0.05). The FCM results showed that the apoptotic rates of SKOV3 cells in combined groups were higher than those in MLT groups and 50.0mg·L^-1 CBP group(P<0.05). The apoptotic rate of SKOV3 cells in 2 mmol·L^-1MLT+ 50.0 mg·L^-1 CBP group was (58.9±2.0)% which was higher than that in 50.0mg·L^-1 CBP group (P<0.05).The expression levels of Bax gene in combined groups were increased(P<0.05),and the expression levels of Bcl-2 gene were decreased (P<0.05)compared with CBP groups with the same doses. Conclusion: MLT can enhance the inhibitory effect of proliferaion and apoptosis induction of CBP on the ovarian cancer SKOV3 cells in vitro. It induces the apoptosis of SKOV3 cells through enhancing the Bax expression and down-regulating the Bcl-2 expression.