Histone deacetylase inhibitors induce human renal cell carcinoma cell apoptosis through p-JNK activation
- VernacularTitle:组蛋白去乙酰化酶抑制剂通过激活p-JNK信号通路诱导肾癌细胞凋亡
- Author:
Miqing XU
1
;
Ming HONG
;
Hui XIE
Author Information
1. 广州医科大学附属第二医院内科
- Keywords:
apoptosis;
cell cycle;
histone deacetylase inhibitor;
human renal cell carcinoma;
LBH589;
trichostatin A
- From:
Journal of Southern Medical University
2013;(10):1409-1415
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of histone deacetylase inhibitors trichostatin A (TSA) and LBH589 on the growth of human renal cell carcinoma OS-RC-2 cells in vitro and explore the underlying molecular mechanism. Methods OS-RC-2 cells were treated with LBH589 or TSA with or without SP600125 pretreatment, and the cell viability was measured by MTT assay. The changes of cell cycle distribution and apoptosis of OS-RC-2 cells were examined by flow cytometry, and the expressions of c-Jun, p-c-Jun, Bcl-2, and Bax were quantified by Western blotting. Results TSA and LBH589 both inhibited the growth of OS-RC-2 cells in a dose-and time-dependent manner. TSA at 1μnmol/L and LBH589 at 50 nmol/L caused obvious cell cycle arrest in G2/M phase and cell apoptosis, and significantly increased the protein levels of phosphorylated c-Jun. TSA treatment obviously increased Bax expression but decreased Bcl2 expression in the cells. The growth inhibitory effect of TSA was attenuated by the JNK inhibitor SP600125 in OS-RC-2 cells. TSA-induced phosphorylation of c-Jun and Bax upregulation was partially counteracted by SP600125. Conclusion TSA and LBH589 can cause cell cycle arrest and induce apoptosis in OS-RC-2 cells, in which process P-JNK pathway plays an important role.
