Role of P21 protein and survivin on apoptosis-inducing effect by mevastatin against NSCLC cells
- VernacularTitle:P21蛋白和生存素在美伐他汀诱导人非小细胞肺癌凋亡中的作用
- Author:
Liping GUO
;
Jianmin LUO
- Publication Type:Journal Article
- Keywords:
mevastatin;
carcinoma,non-small cell lung;
apoptosis;
oncogene protein p21;
survivin
- From:
Medical Journal of Chinese People's Liberation Army
2001;0(09):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of P21 protein and survivin on the cell apoptosis of non-small cell lung cancer (NSCLC) induced by mevastatin. Methods The inhibitory effect of mevastatin on A549 and NCI-H520 cell line was evaluated by MTT assay. The cell cycle distribution and apoptosis induction were determined with flow cytometer and transmission electron microscope. The expression of p21 protein was assessed with flow cytometer. The mRNA expression of p21 and survivin was assessed with RT-PCR. Results Flow cytometry showed that mevastatin induced G_0/G_1 cell arrest in NSCLC cell lines. The results indicated that mevastatin caused apoptosis in concentration-dependent manner. Mevastatin produced no change in expression of P21 mRNA and total P21 protein. Concomitantly, P21 protein localized on cellular membrane was decreased. It was also found that mevastatin suppressed the expression of survivin mRNA in NSCLC cell lines. All these effects were reversed by mevalonate. Conclusions Mevastatin inhibited the proliferation of NSCLC cell lines. Mevastatin exerts growth inhibitory effect and induces apoptosis effect by inhibiting mevalonate synthesis. Its mechanisms might involve blockade of the isoprenylation of p21 protein and down-regulation of the expression of survivin mRNA.