[Effect of a novel EZH2 inhibitor GSK126 on prostate cancer cells].

Zhejiang Da Xue Xue Bao Yi Xue Ban 2016 May;45(4):356-363

School of Medicine, Zhejiang University City College, Hangzhou 310015, China.

To investigate the effect of a novel EZH2 inhibitor GSK126 on cell growth, apoptosis and migration of prostate cancer cells. Prostate cancer PC-3 and DU145 cells were treated with GSK126 at different doses. Cell growth was detected by sulforhodamine assay. Cell apoptosis was assayed by Annexin V-/PI kit. Transwell chamber and wound healing assays were conducted to detect cell migration. The mRNA level was detected by quantitative PCR, and protein expression was detected by Western blot analysis. GSK126 showed significant effect on cell growth and apoptosis when the dose was higher than 50 μmol/L. Wound healing assay revealed that scratch space in PC-3 cells was significantly increased in a dose-dependent manner in GSK126-treated groups[(247.2±24.4),(347.2±19.2) and (410.5±18.1) μm in low, medium and high dose (5.0, 20.0, 50.0 μmol/L), respectively] as compared with the control group[(171.3±17.8) μm](all <0.05). Transwell assay showed that migrated PC-3 cells in control group was 322.0±17.9,while those in GSK126-treated groups were 198.3±15.4 (low),82.7±6.2 (medium) and 30.2±4.1 (high), and the differences between the control group and GSK126-treated groups were significant(all <0.05). In addition, GSK126 up-regulated E-cadherin mRNA expression and down-regulated N-cadherin and Vimentin mRNA expression, whereas had no significant effect on Snail, Fibronectin and VEGF-A mRNA expression. The protein expression of E-cadherin was elevated but VEGF-A protein did not change in GSK126-treated groups. Similar results were exhibited in DU145 cell. GSK126 can significantly inhibit cell migration and invasion in prostate cancer PC-3 and DU145 cells, which may be resulted from its effect on epithelial-mesenchymal transition. GSK126 may be used as a potential anti-prostate cancer dug in clinic.

Download full-text PDF

Source
May 2016
29 Reads

Publication Analysis

Top Keywords

cell growth
12
prostate cancer
12
inhibitor gsk126
8
growth apoptosis
8
gsk126 cell
8
ezh2 inhibitor
8
novel ezh2
8
wound healing
8
cell
5
protein expression
4
expression detected
4
detected western
4
analysis gsk126
4
higher μmol/l
4
μmol/l wound
4
dose higher
4
apoptosis dose
4
blot analysis
4
western blot
4
detected quantitative
4

Similar Publications