王蒲雄志,夏光慨,卢家俊,袁周,史向军,黄新余
WANG Puxiongzhi,XIA Guangkai,LU Jiajun,YUAN Zhou,SHI Xiangjun,HUANG Xinyu

• 1:上海交通大学附属第六人民医院肝胆胰外科

摘要(Abstract)：

目的:分析聚腺苷二磷酸核糖聚合酶(PARP)抑制剂对胰腺癌细胞的抗肿瘤机制及耐药性。方法:将人胰腺癌顺铂耐药细胞株PATU-8988/DDP细胞分为对照组、PARP抑制组、联合顺铂组,对照组细胞加入DMEM培养液培养24 h,PARP抑制组细胞加入10μmmol/L PARP抑制剂AG014699培养,联合顺铂组细胞加入10μmmol/L PARP抑制剂AG014699及10 mg/L顺铂培养; 3组细胞培养24 h后,采用MTT法检测各组细胞的增殖率,流式细胞术检测各组细胞的凋亡率,Western blot法检测各组细胞中PARP蛋白表达水平。结果:3组细胞培养24 h时的增殖率比较,联合顺铂组 PARP抑制组>对照组,两两比较,差异有统计学意义(P <0. 05); 3组细胞培养24 h时的细胞中PARP蛋白表达水平比较,PARP抑制组及联合顺铂组显著低于对照组,差异有统计学意义(P <0. 05),联合顺铂组与PARP抑制组细胞中PARP蛋白表达水平比较,差异无统计学意义(P> 0. 05)。结论:PARP抑制剂可抑制胰腺癌细胞的增殖及促进胰腺癌细胞凋亡,提高胰腺癌细胞对顺铂的敏感性,其机制可能与PARP抑制剂下调PARP表达有关。
Objective: To investigate the antitumor mechanism and drug resistance of poly ADPribose polymerase( PARP) inhibitor to pancreatic cancer cells. Methods: Cells of human pancreatic cancer cisplatin resistant cell line patu-8988/DDP were divided into control group( group A),PARP inhibition group( group B) and cisplatin combination group( group C). Group A was cultured in DMEM medium for 24 h,group B was cultured with 10 μmmol/L PARP inhibitor AG014699 for 24 h,and group C was cultured with 10 μmmol/L PARP inhibitor AG014699 and 10 μg/m L cisplatin for24 h. After 24 h of cell culture,the proliferation rates of PATU-8988/DDP cells,apoptosis rates of PATU-8988/DDP cells and the PARP protein expression levels in PATU-8988/DDP cells in each group were detected by MTT assay,flow cytometry,and Western blot respectively. Results: The cell proliferation rates were compared among the three groups 24 h after cell culture,it was showed that the cisplatin combination group < PARP inhibition group < control group and the difference was statistically significant when compared in pairs( P < 0. 05). The apoptosis rates were compared among the three groups 24 h after cell culture,it was showed that the cisplatin combination group > PARP inhibition group > control group and the difference was statistically significant when compared in pairs( P <0. 05). The PARP protein expression levels in the cells were compared among the three groups 24 h after cell culture,the PARP inhibition group and the cisplatin combination group were significantly lower than the control group 24 h after cell culture and the difference was statistically significant( P <0. 05); but the PARP protein expression levels between the cisplatin combination group and the PARP inhibition group were compared,there was no statistical significance( P > 0. 05). Conclusion: PARP inhibitors can inhibit the proliferation and promote the apoptosis of pancreatic cancer cells as well as can improve the sensitivity of pancreatic cancer cells to cisplatin and enhance the chemical toxicity of cisplatin to pancreatic cancer cells. The mechanism may be related to the down-regulation of PARP expression by PARP inhibitors.

关键词(KeyWords)： 胰腺肿瘤;细胞增殖;细胞凋亡;基因表达;聚腺苷二磷酸核糖聚合酶抑制剂;耐药;机制
pancreatic neoplasms;cell proliferation;apoptosis;gene expression;poly ADP-ribose polymerase(PARP) inhibitor;drug resistance;mechanism

Abstract:

Keywords:

基金项目(Foundation): 上海市科学技术委员会科研计划项目(18ZR1429100)

作者(Author): 王蒲雄志,夏光慨,卢家俊,袁周,史向军,黄新余
WANG Puxiongzhi,XIA Guangkai,LU Jiajun,YUAN Zhou,SHI Xiangjun,HUANG Xinyu

DOI: 10.19367/j.cnki.2096-8388.2020.05.010

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