Inhibitory effect of Fk228 on proliferation and invasion of andragon-independent prostate cancer cells

Abstract

Objective To investigate the suppressive effect of Fk228 on growth of prostate cancer cells,and to evaluate the effect of Fk228 on cell invasion and metastasis.Methods The inhibitory effect of Fk228 (2,5,15,30 and 50 nmol/L) on growth of PC-3 cells and its cytotoxicity were examined by using methyl thiazol tetrazolium (MTT) assay,cell cycle arrest was valued by flow cytometry,the expression level of apoptosis and cell adhesion molecule protein was detected by using Western blotting,histone deacetylase (HDAC) colorimetric assay kit was applied to determine the changes of HDAC activity,and cell invasion test was used for detection of the PC-3 cell invasive activity.Results Fk228 obviously inhibited proliferation of PC-3 cells,the survival rate of cells was declined to about 55％ after Fk228 (15 nmol/L)treatment for 15 h,and cell cycle was arrested in sub-G0 phase (0.50％ and 0.65％ to 16.50％ and 28.10％,respectively).Cell in S phase declined (18.00％ and 16.50％ to 10.00％ and 4.35％,respectively).The expression levels of apoptosis protein Caspase-3 and poly ADP-ribose polymerase (PAR P) were increased,the expression levels of E-cadherin,intercellular adhesion molecule-1 (ICAM-1) and VCAM-1 were declined,and the invasive ability was reduced.Conclusion Fk228 can inhibit proliferation of prostate cancer cells in vitro,induce cell apoptosis by activation of Caspase-3,and reduce invasive ability by regulating the expression of ICAM-1. Key words: Prostate cancer; Histone deacetylase inhibitor; Proliferation; Invasion