Abstract:

Abstract:Objective
To observe the influence of sirtinol，a silent information regulator 1(SIRT1) inhibitor,in the cell proliferation,cell cycle progression and the expression levels of positive regulator proteins of the cell cycle including Cyclin D1，CDK4  and pRb  in prostate cancer DU145 cells,and to explore the possible mechanism of SIRT1 in  occurrence of prostagte cancer.Methods The DU145 cells at logarithmic growth phase were cultured in vitro and divided into control group（DMSO）and different doses (10,25,50  μmol?L-1) of sirtinol  groups.The inhibitory rate of  growth of DU145 cells was detected with MTT method,the SIRT1 mRNA and protein expression levels were determined by RT-PCR and Western blotting method,and the cell cycle was measured by flow cytometry.The Cyclin D1，CDK4 and pRb protein expression levels were examined by Western blotting method.Results Compared with control group，the inhibitory rates of growth of the DU145 cells in different doses of sirtinol groups were increased markedly in a dose-dependent manner（P<0.01）,and the flow cytometry analysis result showed the DU145 cells at G1 phase were increased（P<0.01）.Compared with control group，the expression levels of SIRT1 mRNA and protein in DU145 cells in different doses of sirtinol groups were decreased significantly（P<0.01）;the expression levels of  Cyclin D1 and pRb proteins were decreased（P<0.01）,whereas the expression levels of CDK4 had no change（P>0.05）.Conclusion SIRT1 inhibition by sirtinol can inhibit the cell growth of prostate cancer DU145 cells in a dose-dependent manner and arrest the cell cycle progression，and its mechanism may be related to decreasing the CyclinD1 and pRb protein expressions.

Key words: sirtinol, silent information regulator 1, prostate neoplasms, DU145 cells