曲古霉素对卵巢癌细胞体外增殖与凋亡能力的影响及其分子机制研究

Effects of trichomycin on proliferation and apoptosis of ovarian cancer cells in vitro and its molecular mechanisms

目的研究曲古霉素对卵巢癌细胞增殖、凋亡能力的影响及机制。方法将卵巢癌SKOV-3细胞分为空白组(生理盐水)、对照组(10μg·m L-1顺铂)和低、中、高剂量实验组(1.0,1.5,2.0μmol·L-1曲古霉素)。以噻唑蓝(MTT)检测细胞增殖情况,以Hoechst 33258核染色法检测细胞凋亡,以JC-1染色法检测细胞线粒体膜电位(MMP),以蛋白质印迹法(WB)检测细胞凋亡相关蛋白的表达。结果空白组、对照组和低、中、高剂量实验组凋亡率分别为(1.26±0.35)%,(25.48±2.52)%,(22.65±2.67)%,(29.15±3.34)%,(58.25±3.93)%,MMP分别为1.00±0.00,0.72±0.15,0.80±0.05,0.62±0.07,0.51±0.05,Caspase-3蛋白相对表达量为1.46±0.25,0.48±0.06,1.32±0.16,0.85±0.11,0.35±0.09,p53蛋白相对表达量为1.58±0.33,0.63±0.21,1.46±0.29,1.05±0.16,0.58±0.14,Bax蛋白相对表达量为0.56±0.12,0.91±0.05,0.89±0.22,0.92±0.15,1.32±0.20,Bcl2蛋白相对表达量为0.93±0.14,0.46±0.02,0.71±0.05,0.62±0.03,0.56±0.04,差异均有统计学意义(均P<0.05)。结论曲古霉素可抑制卵巢癌细胞的增殖,通过调控凋亡通路相关蛋白及线粒体凋亡途径诱导癌细胞凋亡,且与干预剂量相关。

Objective To investigate the effect and mechanism of trichomycin on proliferation and apoptosis of ovarian cancer cells.Methods SKOV-3 cells of ovarian cancer were divided into blank group(treated with saline),control group(10μg·mL-1cisplatin)and low,middle,high dose experimental groups(treated with trichomycin of 1.0,1.5,2.0μg·mL-1).Cell proliferation inhibition and apoptosis were detected by MTT and Hoechst 33258 nuclear staining respectively.Mitochondrial membrane potential(MMP)were detected by by JC-1 staining;the expression of apoptosis-related protein were detected by Western blot(WB).Results The apoptotic rates of blank group,control group and low,middle,high dose experimental groups were(1.26±0.35)%,(25.48±2.52)%,(22.65±2.67)%,(29.15±3.34)%,(58.25±3.93)%,MMP were 1.00±0.00,0.72±0.15,0.80±0.05,0.62±0.07,0.51±0.05,the relative expression of protein Caspase-3 were 1.46±0.25,0.48±0.06,1.32±0.16,0.85±0.11,0.35±0.09,the relative expression of protein p53 were 1.58±0.33,0.63±0.21,1.46±0.29,1.05±0.16,0.58±0.14,the relative expression of protein Bax were 0.56±0.12,0.91±0.05,0.89±0.22,0.92±0.15,1.32±0.20,the relative expression of protein Bcl2 were 0.93±0.14,0.46±0.02,0.71±0.05,0.62±0.03,0.56±0.04,the difference was all statistically significant(all P<0.05).Conclusion Trichomycin can inhibit the proliferation of ovarian cancer cells,induce apoptosis by regulating apoptotic pathway related proteins and mitochondrial apoptotic pathways,and is related to the intervention dose.