Study On The Effect And Mechanisms Of Histone Deacetylase Inhibitors On The Proliferation And Invasion Of Prostate Cancer Cells

Part I The expression and potential application of histone deacetylase in prostate cancer.Objective To investigate the expression and activity of histone deacetylase(HDAC) in prostate cancer and assess potential application of histone deacetylase inhibitor in china.Methods The expression of HDAC was detected by Western blotting in 37 prostate cancer,27 benign prostatic hyperplasia. The colorimetric Assay kit was used to determine the HDAC activity. The difference of HDAC activity in benign prostatic hyperplasia and prostate cancer was analyzed by statistics. The correlation of HDAC expression level and values of PSA and Gleason score has also been assessed.Results HDACs were overexpressed in most case of prostate cancer, the expression rates were HDAC1:56.8%, HDAC2:67.6%, HDAC3:83.8% and HDAC4:72.9%, respectively; there were significant difference between prostate cancer and benign prostatic hyperplasia in HDAC activity (P<0.05); the expression level of HDAC does not correlate with the values of PSA and Gleason score.Conclusions HDAC was highly expressed in prostate cancer, suggesting that HDAC might be a potentail target for the management of prostate cancer in chinese patients, HDAC inhibitors could be a new therapeutic agent in future clinics.Part II Effect of Fk228 on the proliferation and invasion of prostate cancerObjective To investigate the suppressive effect of Fk228 on prostate cell growth, and to evaluate the effect of cell invasion and metastasis.Methods The inhibition effect of Fk228 on PC-3 cell growth and its cytotoxicity were carried out by MTT test; cell cycle arrest was valued by flow cytometry assay; the expression level of apoptosis and cell adhesion molecule protein were confirmed by Western blotting; HDAC colorimetric Assay kit to determine the changes of HDAC activity; and cell invasion test for detection of the PC-3 cell invasive activity.Results Fk228 obviously inhibited PC-3 cell proliferation, survival cell declined to 50% after 48 hour of fk228 treatment in 20 nM, cell cycle arrested in sub-G1 phase. The expression of apoptosis protein caspase-3 and PARP were increased, and associated with E-cadherin. ICAM-1 and VCAM-1 expression was declined, so as the cell invasive activity. Conclusions Fk228 can inhibit PC-3 proliferation in vitro, induce cell apoptosis by activation of caspase-3, and reduce cell invasive activity.