FK228 blocks cells survival signal pathways and induces apoptosis of prostate cancer DU145 cells
- VernacularTitle:FK228阻断细胞生存信号通路诱导前列腺癌细胞凋亡
- Author:
Ming ZHAO
;
Sheng-Yu WANG
;
Chun-Mei HOU
;
Zhi-Yan DU
;
Yuan-Ji XU
;
Xiao-Dan YU
;
- Publication Type:Journal Article
- Keywords:
histone deacetylase;
FK228;
heat shock protein 90;
apoptosis;
prostate cancer
- From:
Chinese Journal of Cancer Biotherapy
1995;0(02):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the underlying mechanism of histone deacetylase (HDAC) inhibitor FK228-in- duced apoptosis of the prostate cancer cell line DU145.Methods:The inhibitory effect of FK228 on DU145 cell growth and its cytotoxicity were determined by MTT assay;cell cycle arrest was detected by flow cytometry assay;morphological change was observed by Giemsa staining;and defined kinase protein levels were determined by Western blot analysis.Re- suits:FK228 obviously inhibited DU145 cells growth,arrested cell cycle at G_0/G_1 phase,induced cells morphological changes and degraded several kinase proteins,including EGFR,Her2,Raf-1,Src,Cdk4 and IAP member Survivin.The degradation of these kinases blocked Raf-Mek-Erk and PI3K/Akt survival signal pathways,inducing apoptosis.Condu- sion:FK228 may induce DU145 cell apoptosis through depletion of multiple kinase proteins and blockade of survival sig- nal pathways of DU145 cells.
