奥曲肽抑制雄激素非依赖性前列腺癌增殖的相关分子机制

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目的探讨奥曲肽在体外抑制人雄激素非依赖性前列腺癌细胞DU145增殖作用及相关分子机制。方法以紫杉醇为对照,采用XTT法测定1000nmol/L奥曲肽对DU145细胞增殖的影响,采用人全基因表达谱芯片检测奥曲肽对DU145细胞作用前后基因表达的差异。结果奥曲肽显著抑制前列腺癌DU145细胞的增殖,抑制率(51.4±3.2)%。芯片分析结果显示,奥曲肽对DU145细胞作用前后,共有325个基因有差异表达;其中,表达量差异在2倍以上的基因58个。与增殖相关的基因p21和p27表达升高,Cyclin E和CDK2基因表达降低。结论奥曲肽能在体外抑制雄激素非依赖性前列腺癌细胞DU145的增殖;其作用机制可能与上调p21和p27基因的表达,下调Cyclin E和CDK2基因表达相关。奥曲肽有可能成为治疗雄激素非依赖性前列腺癌的药物选择。 Objective To investigate the inhibitory effect of octreotide on proliferation of human androgen-independent prostate cancer cell line DU145 in vitro and related molecular mechanisms. Methods Paclitaxel was used as a control. The effect of 1000nmol / L octreotide on the proliferation of DU145 cells was determined by XTT method. The gene expression profiles of DU145 cells were detected by human total gene expression microarray. Results Octreotide significantly inhibited the proliferation of prostate cancer DU145 cells with a inhibitory rate (51.4 ± 3.2)%. Chips analysis showed that before and after octreotide treatment DU 325 cells, a total of 325 genes were differentially expressed; Among them, the expression of more than two times more than 58 genes. Proliferation-related genes p21 and p27 expression increased, Cyclin E and CDK2 gene expression decreased. Conclusions Octreotide can inhibit the proliferation of androgen-independent prostate cancer cell DU145 in vitro. The mechanism may be related to up-regulating the expression of p21 and p27 genes and down-regulating the expression of Cyclin E and CDK2. Octreotide may be the drug of choice for the treatment of androgen-independent prostate cancer.
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