Hou Zhenyu, Cui Yunfeng, Xing Huizhi, Mu Xiaoyan
The Second Department of Surgery, Nankai Hospital, Tianjin Medical University, Tianjin 300162, P.R. China.
Department of General Surgery, The Affiliated Hospital, Logistics University of CATF, Tianjin 300162, P.R. China.
Oncol Lett. 2018 Feb;15(2):1943-1948. doi: 10.3892/ol.2017.7500. Epub 2017 Nov 29.
The present study investigated whether poly(ADP-ribose) polymerase (PARP) has an effect on p53-regulated pancreatic cancer. The results of the present study demonstrated that the expression of PARP affects proliferation and apoptosis of pancreatic cancer cells. Olaparib was used to suppress the expression level of PARP-1 in PanC-1 cells. Decreased expression of PARP-1 suppressed cell proliferation and induced apoptosis of PanC-1 cells when compared with controls. Furthermore, decreased expression of PARP-1 resulted in decreased levels of pro-caspase-3 expression, increased caspase-3 activity, suppressed B-cell lymphoma 2 (Bcl-2) protein expression and increased p53 protein expression in PanC-1 cells. Subsequently, ataxia telangiectasia mutated (ATM) activity was inhibited alongside down-expression of PARP-1 resulting in significantly decreased cellular viability of PanC-1 cells, increased p53 protein expression, decreased expression of pro-caspase-3, increased caspase-3 activity and suppressed Bcl-2 protein expression, when compared with PARP-1 suppression alone. Overall, the data confirmed that down-expression of PARP-1 suppressed cell proliferation and induced apoptosis of pancreatic cancer via ATM-deficient p53 signaling pathway.
本研究调查了聚（ADP - 核糖）聚合酶（PARP）是否对p53调节的胰腺癌有影响。本研究结果表明，PARP的表达影响胰腺癌细胞的增殖和凋亡。奥拉帕尼用于抑制PanC - 1细胞中PARP - 1的表达水平。与对照组相比，PARP - 1表达降低抑制了PanC - 1细胞的增殖并诱导其凋亡。此外，PARP - 1表达降低导致PanC - 1细胞中前半胱天冬酶 - 3表达水平降低、半胱天冬酶 - 3活性增加、B细胞淋巴瘤2（Bcl - 2）蛋白表达受到抑制以及p53蛋白表达增加。随后，与单独抑制PARP - 1相比，共济失调毛细血管扩张症突变（ATM）活性与PARP - 1的下调同时受到抑制，导致PanC - 1细胞的细胞活力显著降低、p53蛋白表达增加、前半胱天冬酶 - 3表达降低、半胱天冬酶 - 3活性增加以及Bcl - 2蛋白表达受到抑制。总体而言，数据证实PARP - 1的下调通过ATM缺陷的p53信号通路抑制胰腺癌细胞增殖并诱导其凋亡。
