Inhibitory effect of Akt inhibitor deguelin on the growth of PC-3 prostate cancer cells.
- Author:
Hong-Bo CHEN
1
;
Xiao-Hui HU
;
Ke-Hua JIANG
;
Sheng-Liang ZHU
;
Chun-Xiong ZHAO
;
Wei YUAN
;
Yong LAN
;
Su CHEN
;
Hong-Gang YUAN
;
Xing-Fu SONG
;
Yan-Lin WANG
Author Information
- Publication Type:Journal Article
- MeSH: Cell Line, Tumor; Cell Proliferation; drug effects; Glycogen Synthase Kinase 3; metabolism; Glycogen Synthase Kinase 3 beta; Humans; Male; Prostatic Neoplasms; metabolism; Proto-Oncogene Proteins c-akt; antagonists & inhibitors; Proto-Oncogene Proteins c-mdm2; metabolism; Rotenone; analogs & derivatives; pharmacology
- From: National Journal of Andrology 2013;19(6):501-505
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the inhibitory effect of Akt inhibitor deguelin on PC-3 human prostate cancer cell lines and its possible mechanism.
METHODSPC-3 human prostate cancer cells were cultured in deguelin at the concentrations of 10, 100, 500 and 1 000 nmol/L for 24, 48 and 72 hours, respectively. Then the inhibitory effect of deguelin on the proliferation of the PC-3 cells was determined by MTT assay and that on the cell cycle was detected by flow cytometry. The expression levels of MDM2 and GSK3beta mRNA were measured by RT-PCR and those of MDM2 and GSK3beta proteins by Western blot.
RESULTSAt 24, 48 and 72 hours, the inhibition rates of deguelin on the proliferation of the PC-3 prostate cancer cells were (91.10 +/- 3.75), (86.39 +/- 1.16) and (79.51 +/- 2.63)% at 10 nmol/L, (82.46 +/- 3.65), (76.84 +/- 0.97) and (69.69 +/- 2.30) % at 100 nmol/L, (81.46 +/- 0.41), (75.56 +/- 1.12) and (54.07 +/- 3.21)% at 500 nmol/L, and (66.77 +/- 2.82), (58.22 +/- 0.35) and (39.34 +/- 2.40)% at 1000 nmol/L, all with statistically significant differences from the control group (P < 0.01). Deguelin at 10, 100, 500 and 1 000 nmol/L increased the cell cycles blocked in the G0/G1 phase ([62.4 +/- 2.2], [63.6 +/- 1.1 ], [65.0 +/- 0.3] and [66.5 +/- 1.9]%, P < 0.01) and reduced the percentage of the S-phase cells ([14.7 +/- 2.4], [11.1 +/- 5.2], [5.8 +/- 1.1] and [7.0 +/- 0.6]%, P < 0.01). RT-PCR and Western blot showed markedly up-regulated expressions of GSK3 P3 a3beta down-regulated expressions of MDM2 mRNA and proteins in the PC-3 cells treated with deguelin.
CONCLUSIONAkt inhibitor deguelin can inhibit the proliferation of PC-3 human prostate cancer cells by affecting the down-stream signal molecules GSK3P3 and betaDM2 in the Akt pathway.