title: [Effect of a novel EZH2 inhibitor GSK126 on prostate cancer cells].
abstract: Objective:To investigate the effect of a novel EZH2 inhibitor GSK126 on cell growth, apoptosis and migration of prostate cancer cells.Methods: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.Results: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](allP<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(allP<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.Conclusion: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.
authors.affiliation: Department of Internal Medicine, Taizhou Cancer Hospital, Wenling 317502, China.
authors.forename: Weiren
authors.initials: W
authors.lastname: Lin
authors.affiliation: School of Medicine, Zhejiang University City College, Hangzhou 310015, China.
authors.forename: Yatian
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Medicine, Zhejiang University City College, Hangzhou 310015, China.
authors.forename: Linghui
authors.initials: L
authors.lastname: Zeng
authors.affiliation: Department of Internal Medicine, Taizhou Cancer Hospital, Wenling 317502, China.
authors.forename: Rongbiao
authors.initials: R
authors.lastname: Ying
authors.affiliation: School of Medicine, Zhejiang University City College, Hangzhou 310015, China. zhuf@zucc.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
mesh_terms: D015703:Antigens, CD; D017209:Apoptosis / Q000187:drug effects; D015820:Cadherins / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D005353:Fibronectins / Q000032:analysis / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000737:chemistry / Q000235:genetics / Q000503:physiopathology*; D011728:Pyridones / Q000494:pharmacology*; D012333:RNA, Messenger; D015854:Up-Regulation / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis / Q000187:drug effects; D014746:Vimentin / Q000032:analysis / Q000187:drug effects / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D005353:Fibronectins; C577920:GSK-2816126; D007211:Indoles; D011728:Pyridones; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D014746:Vimentin; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein