Su Shan, Lin Xueyan, Ding Ning, Zhang Hong, Zhang Qinghua, Ding Yumei, Hou Xiaoman, Tian Yongjie
Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong University, Shangdong, China; Department of Gynecology, The Central Hospital of Zibo, Shangdong, China.
Department of Obstetrics and Gynecology, Provincial Hospital Affiliated to Shandong University, Shangdong, China.
Pharmacol Rep. 2016 Dec;68(6):1225-1229. doi: 10.1016/j.pharep.2016.08.001. Epub 2016 Aug 2.
To assess the effects of the poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor PJ34 and ERK1/2 inhibitor U0126 on the proliferation and epithelial mesenchymal transitions (EMT) of cisplatin resistant ovarian cancer SKOV-3 cells.
Proliferation of SKOV-3 cells was evaluated using a 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium bromide assay with PJ34 and U0126 treatment. Expression changes of E-cadherin and vimentin with PJ34 and U0126 treatment was examined using Western blot and quantitative PCR. In addition, invasion assay was performed in cells treated with PJ34 and U0126.
PJ34 and U0126 inhibited proliferation of SKOV-3 cells in a time dependent manner. PJ34 and U0126 suppressed the expression of vimentin and enhanced the expression of E-cadherin. PJ34 and U0126 reduced cell invasion. The inhibitory effects of PJ34 and U0126 were stronger than PJ34 alone. PJ34 inhibited the proliferation and invasion of SKOV-3 cells which can be enhanced by ERK1/2 inhibitor U0126.
These inhibitory effects are partially due to PARP-1 and ERK1/2 mediated attenuation of EMT activity.
评估聚（ADP - 核糖）聚合酶 -1（PARP -1）抑制剂PJ34和细胞外信号调节激酶1/2（ERK1/2）抑制剂U0126对顺铂耐药的卵巢癌细胞SKOV -3增殖和上皮间质转化（EMT）的影响。
采用3 -（4,5 - 二甲基噻唑 -2 - 基）-2,5 - 二苯基四氮唑溴盐法评估PJ34和U0126处理后SKOV -3细胞的增殖情况。使用蛋白质免疫印迹法和定量聚合酶链反应检测PJ34和U0126处理后E - 钙黏蛋白和波形蛋白的表达变化。此外，对经PJ34和U0126处理的细胞进行侵袭实验。
PJ34和U0126以时间依赖性方式抑制SKOV -3细胞的增殖。PJ34和U0126抑制波形蛋白的表达并增强E - 钙黏蛋白的表达。PJ34和U0126减少细胞侵袭。PJ34和U0126联合使用的抑制作用强于单独使用PJ34。PJ34抑制SKOV -3细胞的增殖和侵袭，而ERK1/2抑制剂U0126可增强这种抑制作用。
这些抑制作用部分归因于PARP -1和ERK1/2介导的EMT活性减弱。
