基于"瘀"、"毒"病机探讨西黄丸靶向AR/mTOR信号轴重塑前列腺癌血管形态正常化的机制研究

雄激素受体（AR）异常活跃偶联mTOR信号通路激活，参与肿瘤微环境与血管形态重塑是去势抵抗性前列腺癌（CRCP）发展进程的关键环节，诠释其分子机理有望为CRCP干预治疗奠定新的理论依据。基于前列腺癌（PCa）中医“瘀“、”毒”病机和我们前期研究发现，本研究着眼“肿瘤血管正常化”视角，以AR/mTOR双信号通路为靶点，拟从以下三个方面展开研究：（1）AR抑制后mTOR/VEGF通路代偿性激活诱导CRPC发生机制的假说验证；（2）西黄丸活性成分群对AR/mTOR双信号通路调控的作用机制研究；（3）以“活血”-血管正常化、“解毒”-改善微环境模式入手，探索西黄丸活性成分群介导mTOR/VEGF信号通路推动血管正常化重构肿瘤微环境（TME），从而抑制CRCP进程的分子机制。研究结果阐释和丰富中医“瘀”、“毒”的现代科学内涵，并为临床应用西黄丸治疗CRCP提供实验基础。

The key link in the development process of castration-resistant prostate cancer (CRCP) is the abnormally active androgen receptor (AR) coupled with mTOR signaling pathway activation, participating in tumor microenvironment and vascular morphology remodeling. The interpretation of the molecular mechanism of this link is expected to lay a new theoretical basis for CRCP intervention therapy. Based on the prostatic cancer (PCa) Chinese medicine “stasis” and "toxin" pathogenesis and our previous research findings, this study focuses on the perspective of "tumor blood vessel normalization" and takes the AR/mTOR dual signal pathway as the target, and plans to conduct research from the following three aspects: (1) Hypothesis testing of the mechanism of CRPC induced by compensatory activation of mTOR / VEGF pathway after AR inhibition; (2) Study on the mechanism of the active ingredient group of Xihuang pills on the regulation of AR/mTOR dual signaling pathway; (3) Starting with the "blood circulation" -vascular normalization and "detoxification" -improvement of microenvironment mode, to explore the molecular mechanism of the active ingredient group of Xihuang pills to mediate mTOR / VEGF signaling pathway, promote the normalization of blood vessels to reconstruct the tumor microenvironment (TME), and thus inhibit CRCP process. The research results explain and enrich the modern scientific connotation of "blood stasis" and "toxin" in traditional Chinese medicine, and provide an experimental basis for the clinical application of Xihuang pills in the treatment of CRCP.