The role of lipid metabolism in prostate cancer

为了阐明血脂在前列腺癌中的作用，进行了各种基础研究。首先对甲氧戊酸途径中的关键酶--角鲨烯合成酶进行了研究。我们先前的研究表明，编码角鲨烯合成酶的FDFT1的SNP与前列腺癌的发生风险有关。目前的研究表明，下调FDFT1基因的表达可显著抑制肿瘤的增殖。此外，FDFT1基因表达水平与前列腺癌的生物学侵袭性相关。接下来，评价他汀类药物对低密度脂蛋白受体的影响。前列腺癌细胞是他汀类药物的靶点。他汀类药物调节低密度脂蛋白受体的表达和细胞中的胆固醇含量。这些调节事件与前列腺癌的增殖有关。最后对二甲双胍的疗效进行了评价。二甲双胍通过下调IGF1受体抑制前列腺癌增殖。

Various basic studies were conducted to elucidate the effect of lipids on prostate cancer. First, squalene synthase, which is the key enzyme in mevalonate pathway is evaluated. Our previous study revealed that the SNP of FDFT1, which encodes squalene synthase, was associated with risk of prostate cancer development. The present study showed that down-regulation of FDFT1 gene expression led to significant inhibition of cancer proliferation. Furthermore, the FDFT1 gene expression levels were correlated with biological aggressiveness of prostate cancer. Next, the effect of statin was evaluated as to LDL receptor. Prostate cancer cells were the target of statin. Statin regulated both LDL receptor expression profiles and cholesterol content in the cell. These regulatory events were relevant to prostate cancer proliferation. Finally, the effect of metformin was evaluated. Metformin inhibit prostate cancer proliferation via down-regulation of IGF1-receptor.