Survivin Is Associated With Cell Proliferation and Has a Role in 1a,25-Dihydroxyvitamin D3 Induced Cell Growth Inhibition in Prostate Cancer
Survivin Is Associated With Cell Proliferation and Has a Role in 1a,25-Dihydroxyvitamin D3 Induced Cell Growth Inhibition in Prostate Cancer
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DOI：
10.1016/j.juro.2010.12.005
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发表时间：
2011-04-01
影响因子：
6.6
通讯作者：
Suzuki, Kazuhiro
中科院分区：
文献类型：
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作者：
Koike, Hidekazu;Morikawa, Yasuyuki;Suzuki, Kazuhiro
目的：1 α，25-二羟维生素D-3抑制前列腺癌细胞增殖。Survivin是凋亡抑制蛋白家族的一员。一些研究表明，生存素下调敏感的人类肿瘤细胞的不同组织学来源的常规化疗药物。我们评估了生存素基因表达对前列腺癌细胞体外和体内增殖的影响。我们还研究了在1a，25-二羟维生素D-3治疗前列腺癌cells.Materials and Methods中抑制生存素的抗肿瘤增敏作用：我们在体外和体内使用针对生存素的siRNA敲低生存素的基因表达水平。然后，我们评估了生存素的表达在1a，25-二羟维生素D-3治疗，并检查使用siRNA抑制生存素的抗肿瘤增敏作用在1a，25-二羟维生素D-3治疗激素抵抗的前列腺癌cells.Results：在体外和体内siRNA对生存素显着抑制细胞和肿瘤的生长相比，控制siRNA。在LNCaP和PC 3细胞中，1a，25-二羟维生素D-3降低survivin基因表达并抑制细胞增殖。结论：Survivin与前列腺癌细胞增殖密切相关，在1a，25-hydroxyvitamin D-3抑制前列腺癌细胞增殖中起重要作用。在1a，25-二羟维生素D-3治疗激素难治性前列腺癌中，消除生存素似乎是一种潜在的治疗选择。
Purpose: 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.Materials and Methods: 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.Results: 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.Conclusions: 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.