Effect of PARP-1 on cisplatin resistance in breast cancer MCF-7 cells
10.3969/j.issn.1000-4718.2018.02.005
- VernacularTitle:沉默PARP-1对乳腺癌细胞MCF-7顺铂耐药的影响
- Author:
Jin-Xia LI
1
;
Li MA
Author Information
1. 邢台市人民医院产科
- Keywords:
Poly(ADP-ribose)polymerase-1;
Breast cancer;
Cisplatin;
Drug resistance;
Apoptosis;
Extra-cellular signal-regulated kinases
- From:
Chinese Journal of Pathophysiology
2018;34(2):218-224
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To study the effect of poly(ADP-ribose)polymerase-1(PARP-1)on cisplatin resistance of human breast cancer MCF-7 cells and its possible mechanisms.METHODS: The expression of PARP-1 at mRNA and protein levels in MCF-7 cells and MCF-7/DDP cells was determined by real-time PCR and Western blot.The expression of PARP-1 in the MCF-7/DDP cells was blocked by PARP-1 siRNA.The cell viability and apoptosis were detected by the CCK-8 assay and flow cytometry analysis,respectively.Furthermore, the protein levels of PARP-1, Bcl-2, Bax, cleaved caspase-3,caspase-3,cytochrome C(Cyto-C),extracellular signal-regulated kinase(ERK)and phosphorylated ERK(p-ERK)were detected by Western blot.RESULTS:The expression of PARP-1 at both mRNA and protein levels was signifi-cantly up-regulated in the MCF-7/DDP cells.The expression of PARP-1 was increased in the MCF-7 cells treated with cis-platin.Knockdown of PARP-1 induced the apoptosis of MCF-7/DDP cells with an increased sensitivity to cisplatin.Mean-while,knockdown of PARP-1 down-regulated the protein levels of Bcl-2/Bax and p-ERK, but up-regulated the protein levels of cleaved caspase-3 and Cyto-C.After incubated with a specific ERK inhibitor U 0126,the cell viability in PARP-1 siRNA group was down-regulated significantly.CONCLUSION:Knockdown of PARP-1 increases the sensitivity of MCF-7/DDP cells to cisplatin,and promotes the cell apoptosis via mitochondrial apoptosis pathway.The mechanism may be re-lated to the attenuation of ERK signaling pathway by inhibiting phosphorylation of ERK.
