Survivin Is Associated With Cell Proliferation and Has a Role in 1a,25-Dihydroxyvitamin D 3 Induced Cell Growth Inhibition in Prostate Cancer

Abstract

Prostate cancer cell proliferation is inhibited by 1a,25-dihydroxyvitamin D(3). Survivin is a member of the inhibitors of apoptosis protein family. Several studies indicate that survivin down-regulation sensitizes human tumor cells of different histological origins to conventional chemotherapeutic drugs. We assessed the effect of survivin gene expression on the proliferation of prostate cancer cells in vitro and in vivo. We also examined the antitumor sensitization effect of survivin inhibition in 1a,25-dihydroxyvitamin D(3) treatment for prostate cancer cells. We knocked down gene expression levels of survivin using siRNA against survivin in vitro and in vivo. We then assessed survivin expression in 1a,25-dihydroxyvitamin D(3) treatment and examined the antitumor sensitization effect of survivin inhibition using siRNA in 1a,25-dihydroxyvitamin D(3) treatment of hormone resistant prostate cancer cells. In vitro and in vivo siRNA against survivin significantly inhibited cell and tumor growth compared with control siRNA. In LNCaP and PC3 cells 1a,25-dihydroxyvitamin D(3) decreased survivin gene expression and inhibited cell proliferation. However, survivin gene expression and cell proliferation were not inhibited in DU145 cells but after siRNA transfection against survivin DU145 cell proliferation was inhibited by 1a,25-dihydroxyvitamin D(3). Findings suggest that survivin has a significant association with prostate cancer cell proliferation and an essential role in 1a,25-dihydroxyvitamin D(3) induced prostate cancer cell growth inhibition. It seems that the eliminating survivin in 1a,25-dihydroxyvitamin D(3) therapy for hormone refractory prostate cancer is a potential therapeutic option.