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A study of the molecule target treatment about survivin, an apoptosis inhibitor, in the prostate and renal cancer.

细胞凋亡抑制剂生存素分子靶向治疗前列腺癌和肾癌的研究。

基本信息

批准号：
20791101
负责人：
KOIKE Hidekazu
金额：
$ 1.91万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Young Scientists (B)
财政年份：
2008
资助国家：
日本
起止时间：
2008 至 2009
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20791101/
关键词：
前立腺癌腎癌サバイビン

项目摘要

We assessed the effect of survivin gene expression on the proliferation of prostate cancer (Pca) cells, and studied the association of suvivin gene expression levels with the pathological grade of Pca. In Pca cells, decrease of survivin gene expression by transfection of siRNA was accompanied by inhibition of cell proliferation of Pca cells. In prostate biopsy samples, survivin expression level of Pca was significantly higher than that of BPH or Pca after androgen deprivation therapy, and was associated significantly with high-grade cancer.Next, we assessed the effect of survivin gene expression on the proliferation of renal cancer (RCC) cells, and studied the association of suvivin gene expression levels with the clinical stage of RCC. In Caki-1 cells, decrease of Survivin gene expression by transfection of siRNA was accompanied by inhibition of the proliferation. In clinical RCC tissues, survivin expression levels in metastatic stage were significantly higher.1a,25-dihydroxyvitamin D3 (1,25D) inhibits the proliferation of prostate cancer cells. We examined the antitumor sensitization effect due to survivin inhibition in 1,25D treatment for prostate cancer cells. In LNCaP cells, 1,25D decreased survivin gene expression and inhibited cell proliferation. On the other hand, survivin gene expression and cell proliferation in DU145 cells were not inhibited. However, interestingly, after the transfection of siRNA against survivin, DU145 cell proliferation was inhibited by 1,25D.These findings suggest that survivin has a significant association with prostate and renal cancer cell proliferation and plays an essential role in 1,25D-induced cell growth inhibition in prostate cancer. It seems that the elimination of survivin in the therapy against prostate and renal cancer is a potential therapeutic option.

我们评估了生存素基因表达对前列腺癌（Pca）细胞增殖的影响，并研究了生存素基因表达水平与Pca病理分级的关系。在Pca细胞中，通过转染siRNA降低Survivin基因表达伴随着Pca细胞增殖的抑制。在前列腺活检标本中，前列腺癌组织中Survivin的表达水平显著高于前列腺增生组织和雄激素剥夺治疗后的前列腺癌组织，且与高级别癌显著相关。在Caki-1细胞中，通过转染siRNA降低Survivin基因表达伴随着增殖抑制。在临床RCC组织中，转移期Survivin表达水平明显增高。1a，25-二羟维生素D3（1，25 D）抑制前列腺癌细胞增殖。我们研究了在1，25 D治疗前列腺癌细胞中由于生存素抑制引起的抗肿瘤增敏作用。在LNCaP细胞中，1，25 D降低survivin基因表达，抑制细胞增殖。另一方面，DU 145细胞中的survivin基因表达和细胞增殖未受到抑制。结果表明，Survivin与前列腺癌和肾癌细胞增殖密切相关，在1，25 D诱导的前列腺癌细胞增殖抑制中起重要作用。在前列腺癌和肾癌的治疗中消除生存素似乎是一种潜在的治疗选择。