Statins enhance anti-tumro effect of sub reoylanilide hydroxamic acid on human non-small cell lung carcinoma cells
10.3785/j.issn.1008-9292.2015.09.05
- VernacularTitle:洛伐他汀或辛伐他汀协同组蛋白去乙酰化酶抑制剂对人非小细胞肺癌的抑制作用
- Author:
Gui-Kai LIANG
1
;
Zhang-Ting YAO
;
Jie-Qiong ZHANG
;
Xi CHEN
;
Rui-Yang LIU
;
Hui-Hui CHEN
;
Hong-Hai WU
;
Lu JIN
;
Ling DING
Author Information
1. 浙江大学药学院浙江省抗肿瘤药物临床前研究重点实验室
- Keywords:
Carcinoma,non-small-cell lung/drug therapy;
Lovastatin/pharmacology;
Simvastatin/pharmacology;
Drug synergism;
Proto-oncogene proteins p21 ( ras)
- From:
Journal of Zhejiang University. Medical sciences
2015;(5):500-505
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To evaluate the anti-tumor effect of the combination of suberoylanilide hydroxamic acid ( SAHA ) with statins ( lovastatin or simvastatin ) on non-small cell lung carcinoma (NSCLC) cells.Methods: Human NSCLC A549 cells were treated with SAHA in combination of lovastatin or simvastatin .The cell growth was analyzed by SRB method, and the apoptosis of A 549 cells was assessed by flow cytometer .The expression of cleaved poly-ADP-ribose polymerase ( cleaved-PARP) and p21 protein was analyzed by Western-blotting when A549 cells were challenged with 2 .5 μmol/L SAHA and 5 μmol/L lovastatin . Results: Lovastatin and simvastatin synergized SAHA in the inhibition of A549 cells.SAHA induced apoptosis was also enhanced by lovastatin .Treatment with 2.5 μmol/L SAHA significantly up-regulated the expression of p21 protein in 48 h, while the protein expression was reduced in combined treatment with 5 μmol/L lovastatin .Conclusion: Statins can synergize the anti-tumor effect of SAHA in human NSCLC cells through ap 21-dependent way .