Simvastatin inhibits the proliferation of human prostate cancer PC-3 cells via down-regulation of the insulin-like growth factor 1 receptor

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• 作者：Yoshitaka Sekine ; Yosuke Furuya ; Masahiro Nishii ; Hidekazu Koike ; Hiroshi Matsui ; Kazuhiro Suzuki
• 关键词：Statin ; Simvastatin ; IGF-1 ; IGF-1 receptor ; PC-3
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2008
• 出版时间：25 July 2008
• 年：2008
• 卷：372
• 期：2
• 页码：356-361
• 全文大小：567 K

文摘

Recently, statins have been being studied for their proapoptic and antimetastatic effects. However, the exact mechanisms of their anticancer action are still unclear. Dolichyl phosphate is a nonsterol isoprenoid derivative in the mevalonate pathway that affects the expression of the Insulin-like growth factor 1 receptor (IGF-1R). IGF-1R activation is required for prostate cell proliferation; therefore, IGF-1R inhibitory agents may be of preventive and/or therapeutic value. In this study, the effects of simvastatin on IGF-1R signaling in prostate cancer PC-3 cells were examined. Simvastatin suppressed proliferation and induced apoptosis of PC-3, and the expression of IGF-1R was suppressed by simvastatin. Knockdown of IGF-1R by siRNA led to inhibition of proliferation of PC-3. Simvastatin also inhibited IGF-1-induced activation of both ERK and Akt signaling and IGF-1-induced PC-3 cell proliferation. Our results suggest statins are potent inhibitors of the IGF-1/IGF-1R system in prostate cancer cells and may be beneficial in prostate cancer treatment.