NOX通路在氧化应激诱导的宫颈癌细胞凋亡中的作用

Effect of NOX pathway in oxidative stress-induced apoptosis of cervical cancer cells

目的探讨烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NOX)通路在氧化应激诱导的宫颈癌细胞凋亡中的作用。方法流式细胞术检测不同类型宫颈癌细胞内在的总活性氧(ROS)水平及NOX途径抑制剂DPI处理前后不同类型宫颈癌细胞内线粒体途径和NOX途径ROS水平;DPI预处理、H_2O_2作用后采用流式细胞术检测不同类型宫颈癌细胞凋亡率。结果人乳头瘤病毒(HPV)阳性宫颈癌细胞内在ROS水平明显高于HPV阴性宫颈癌细胞(P<0.05),两类宫颈癌细胞线粒体途径来源ROS水平比较差异无统计学意义(P>0.05)。与预处理前比较,DPI预处理后HPV阳性宫颈癌细胞内在ROS水平均明显降低(P均<0.05)。与诱导前及HPV阴性宫颈癌细胞比较,H_2O_2诱导后HPV阳性宫颈癌细胞凋亡率均明显升高,且高于DPI预处理及DPI预处理+H_2O_2诱导细胞(P均<0.05)。结论 NOX通路在HPV感染导致宫颈癌的过程中具有重要作用,促氧化治疗可能更好地杀伤HPV阳性宫颈癌细胞。

Objective To investigate the oxidative stress status of different types of cervical cancer cells, and the role of nicotinamide adenine dinucleotide phosphate oxidase （NOX） pathway in oxidative stress-induced apoptosis of cervical cancer Cells. Methods Flow cytometry （FCM） was employed to detect the levels of total reactive oxygen species （ROS） of different types of cervical cancer cells and intracellular ROS levels derived from mitochondrial and NOX pathway before and after treatment with a NOX inhibitor, DPI. After DPI pretreatment and H2O2 action, flow cytometry was Used to detect the apoptosis rate of different types of cervical cancer cells. Results HPV-positive ceils showed higher levels of ROS as compared with HPV-negative cells （P 〈 0.05 ）. No significant difference was found in the mitochondrial pathway-derived ROS level between HPV-negative ceils and HPV-positive cells （P 〉 0.05）. NOX inhibitor DPI significantly reduced ROS level in HPV-positive Ceils as compared with that before treatment （P 〈0.05 ）. Compared with the control group and the HPV-negative cells, the apoptosis rate of HPV-positive cells increased after H2O2 induction and was higher than that of HPV-positive cells group with DPI pretreatment and with DPI pretreatment ＋ H2O2 induction. Conclusion NOX pathway plays an important role in the process of HPV inducing cervical cancer, and pro-oxidant treatment may be more effective in killing HPV-positive cervical cancer ceils.