低睾酮/肥胖/胰岛素抵抗生物轴在前列腺癌恶性进展中的作用及其分子机制的研究

Testosterone has always been considered as a risk factor for prostate cancer. However, a number of recent clinical studies from abroad find that low testosterone promotes the malignant progress of prostate cancer. Our study found that the lower the serum testosterone level in patients, the higher the malignant degree of tumor. Moreover, there was a significant correlation between the total serum testosterone levels, BMI value and serum insulin levels in patients. Preliminary experiments in vitro demonstrated that prostate cancers appeared a remarkable progression in high insulin environment, which was accompanied by IGF1R signaling pathway activation. Therefore, we speculated that the IGF1R signaling pathway activated by the low testosterone/obesity/insulin resistance biological axis promoted prostate cancer development. In this project，we will firstly find out the correlation between the serum testosterone and clinical index of patients with prostate cancer(BMI，serum insulin，pathological level，stage, and prognosis, etc) in Chinese population.Secondly，we will explore the role and molecular mechanisms of low testosterone/obesity/insulin resistance biological axis in prostate cancer development (proliferation, metastasis, and epithelial-mesenchymal transition, etc), including transcriptional activation, methylated modification, post-transcriptional regulation, and feedback regulation, etc. The results will provide important theoretical basis in prostate cancer including individualized prevention, diagnosis, treatment, prognosis judgement.

睾酮一直被认为是前列腺癌的危险因素。但是，国外多项新近临床研究发现,低睾酮促进前列腺癌的进展。我们的研究发现：患者的血清睾酮水平越低，肿瘤的恶性程度越高；患者的血清总睾酮、体重指数（BMI）、血清胰岛素水平之间有显著的相关性。体外预实验发现：把前列腺癌细胞置于高胰岛素环境中培养，细胞的恶性表型显著增强，并伴有胰岛素样生长因子受体（IGF1R）信号通路的激活。为此我们提出假说：低睾酮/肥胖/胰岛素抵抗生物轴激活的IGF1R信号通路促进前列腺癌的进展。项目拟：（1）明确中国人群前列腺癌患者血清睾酮与临床指标（BMI、胰岛素、病理级别、分期、预后等）的相关性；（2）探索低睾酮/肥胖/胰岛素抵抗生物轴在前列腺癌进展（增殖、转移、上皮间质转化等）中的作用及分子机制(转录激活、甲基化修饰、转录后调控、反馈调控等)。研究结果将为前列腺癌的个体化预防、诊断、治疗、预后判断提供重要的理论依据。

睾酮一直被认为是前列腺癌的危险因素，也是当前前列腺癌研究方面的热点，我们从患者睾酮水平、肥胖、胰岛素抵抗、前列腺癌恶性进展几个方面作为出发点，对该项目的研究得出以下结论：患者的血清睾酮水平越低，肿瘤的恶性程度越高；患者的血清总睾酮、体重指数（BMI）、血清胰岛素水平之间有显著的相关性。体外实验进一步发现：前列腺癌细胞置于高胰岛素环境中培养，细胞的恶性表型显著增强，并伴有胰岛素样生长因子受体（IGF1R）信号通路的激活。我们初步证实：低睾酮/肥胖/胰岛素抵抗生物轴激活的IGF1R信号通路促进前列腺癌的进展，研究结果将为前列腺癌的个体化预防、诊断、治疗、预后判断提供重要的理论依据。