标题：下调PAK5抑制紫杉醇诱导卵巢癌细胞自噬现象的研究

      作者：许红玲 1，张萍 2，李笛悠 2，孙中锋 2，林亚英 2    (1.安庆市立医院妇科，安徽 安庆 246000；2.上海交通大学医学院附属新华医院妇科，上海 200090)

      卷次： 2016年27卷23期

      【摘要】 目的 初步探讨下调PAK5的表达对化疗药物紫杉醇诱导CAOV-3卵巢癌细胞发生自噬和凋亡的影响。方法 通过RT-qPCR检测 PAK5在卵巢癌细胞中的mRNA表达情况。在CAOV-3卵巢癌细胞中通过下调PAK5表达后，CCK8实验检测紫杉醇对肿瘤细胞毒性改变，流式细胞术检测细胞凋亡率的改变，以及免疫印迹法检测自噬相关蛋白LC3B的表达变化。结果 PAK5在不同卵巢癌细胞中高表达；在CAOV-3卵巢癌细胞中，与阴性对照 siRNA组比较，PAK5 siRNA组中无论是PAK5的mRNA水平还是蛋白表达水平均明显降低，差异具有统计学意义(P<0.05)；随着紫杉醇浓度的逐渐递增，紫杉醇对CAOV-3卵巢癌细胞毒性逐渐增加，而下调PAK5表达后，紫杉醇对卵巢癌细胞毒性增加更为明显，差异具有统计学意义(P<0.05)；在紫杉醇处理的CAOV-3卵巢癌细胞中，下调PAK5的表达后可明显增加细胞的凋亡率，差异具有统计学意义(P<0.05)；在紫杉醇处理的CAOV-3卵巢癌细胞中，下调PAK5的表达后可减少自噬相关蛋白LC3B蛋白的表达。结论 PAK5过表达于不同的卵巢癌细胞中，下调PAK5基因可以促使自噬相关蛋白LC3B表达减弱，可能是通过抑制CAOV-3卵巢癌细胞发生自噬，促进细胞凋亡，从而提高了CAOV-3卵巢癌细胞对紫杉醇化疗的敏感性，减少紫杉醇获得性耐药的发生。
      【关键词】 PAK5；卵巢癌；自噬；紫杉醇
      【中图分类号】 R737.31 【文献标识码】 A 【文章编号】 1003—6350（2016)23—3798—04

Downregulation of PAK5 inhibits paclitaxel-induced autophagy in ovarian cancer cells.
XU Hong-ling 1, ZHANGPing 2, LI Di-you 2, SUN Zhong-feng 2, LIN Ya-ying 2. 1. Department of Gynaecology, Anqing Hospital, Anqing 246000,Anhui, CHINA; 2. Department of Gynaecology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School ofMedicine, Shanghai 200090, CHINA
【Abstract】 Objective To investigate the effect of downregulation of PAK5 on paclitaxel-induced autophagyand apoptosis in human ovarian cancer cell line (CAOV-3). Methods PAK5 mRNA quantification in ovarian cancerwas detected by RT-qPCR. In CAOV-3 cells, after down-regulation of PAK5 expression, the change of CAOV-3 cells cy-totoxicity by paclitaxel was detected by Cell Counting Kit-8 (CCK8), and cell apoptosis was detected by flow cytome-try. The expression changes of autophagy-related protein (LC3B) were detected by western blotting. Results The PAK5is overexpressed in ovarian cancer cell line. PAK5-siRNA can significantly downergulate the expression of PAK5 gene inCAOV-3 cells (P<0.05). Silencing PAK5 significantly increases the sensitivity of CAOV-3 cells to paclitaxel (P<0.05).PAK5 knockdown enhances paclitaxel-induced apoptosis in ovarian cancer, and PAK5 silencing reduces paclitaxel-in-duced autophagy in CAOV-3 cells. Conclusion The PAK5 is overexpressed in ovarian cancer cell line, and downregu-lation of PAK5 gene can inhibit LC3B expression and may promote apoptosis through inhibition of autophagy inCAOV-3 cells.
      【Key words】 PAK5; Ovarian cancer; Autophagy; Paclitaxel·论 著·doi:10.3969/j.issn.1003-6350.2016.23.005