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目的探讨磷酸化修饰对p53直接线粒体转移的影响以及在顺铂诱导的卵巢癌细胞凋亡中的作用以及与卵巢癌顺铂耐药的关系。方法应用Western Blot检测顺铂作用前后卵巢癌顺铂敏感细胞OV2008、A2780s和顺铂耐药细胞C13*、A2780cp的线粒体和细胞浆中Smac蛋白含量以及线粒体和全细胞中磷酸化p53(P-p53)的含量,并应用Hoechst染色法检测卵巢癌细胞的凋亡率。结果顺铂能引起卵巢癌敏感细胞OV2008、A2780s线粒体释放Smac至胞浆并引起细胞凋亡,但在C13*和A2780cp中无此反应。顺铂处理后进入卵巢癌敏感细胞线粒体中的p53蛋白为磷酸化的p53。结论顺铂能引起p53转移至线粒体并导致卵巢癌敏感细胞线粒体释放Smac至胞浆,促进卵巢癌细胞的凋亡,并且磷酸化修饰作用可以影响p53的直接线粒体功能,与卵巢癌化疗耐药有关。
OBJECTIVE: To investigate the effect of phosphorylation on the direct mitochondrial transfer of p53 and its role in cisplatin-induced ovarian cancer cell apoptosis and its relationship with cisplatin-resistant ovarian cancer. Methods Western blot was used to detect the mitochondrial and cytosolic Smac protein levels in ovarian cancer cisplatin-sensitive cells OV2008, A2780s and cisplatin-resistant cells C13 *, A2780cp and phosphorylated p53 (P-p53 ), And the apoptosis rate of ovarian cancer cells was detected by Hoechst staining. Results Cisplatin induced ovarian cancer-sensitive cells OV2008, A2780s mitochondria release of Smac to the cytoplasm and cause apoptosis, but in C13 * and A2780cp no such response. The p53 protein that enters the mitochondria of ovarian cancer-sensitive cells after cisplatin treatment is phosphorylated p53. CONCLUSIONS: Cisplatin can induce the transfer of p53 to mitochondria and cause the mitochondria of ovarian cancer-sensitive cells to release Smac to the cytoplasm and promote the apoptosis of ovarian cancer cells. Phosphorylation can affect the direct mitochondrial function of p53 and is associated with chemoresistance of ovarian cancer .