西黄丸介导PI3K/AKT/mTOR/HIF-1α轴调节Warburg效应促前列腺癌血管正常化机制研究

前列腺癌（Prostate Cancer,PCa）异常血管增生导致的高间质压、低氧及酸性微环境是PCa去势抵抗发生的关键环节。PI3K/AKT/mTOR/HIF-1α轴的异常激活是诱导Warburg效应发生，进而促疾病血管异常增生的重要因素。因此，阻断Warburg效应的发生对于延缓PCa进展至关重要。前期研究表明，具“活血解毒”之西黄丸可下调PCa mTOR及HIF-1α相关通路蛋白表达水平。据此本项目提出西黄丸介导PI3K/AKT/mTOR/HIF-1α信号轴调节Warburg效应促PCa血管正常化的假说。本项目拟采用稳定同位素示踪联合代谢组学等技术综合探究西黄丸调控PCa PI3K/AKT/mTOR/HIF-1α信号轴阻断Warburg效应促血管正常化的分子机制及代谢特征。本假说的验证，将有助于揭示PCa代谢改变与肿瘤进展的内在关联，为去势抵抗性PCa的发病机制提供新的视野和契机。

High interstitial pressure, hypoxia and acidic microenvironment caused by abnormal vascular hyperplasia in prostate cancer (PCa) are the key factors of castration resistance in PCa. Abnormal activation of PI3K/AKT/mTOR/HIF-1α axis is an important factor in inducing Warburg effect and promoting vascular dysplasia. Therefore, blocking Warburg effect is very crucial to delay the progression of PCa. Previous studies have shown that Xihuang Pill with " Promoting blood circulation and detoxifying " can down regulate the expression levels of PCa mTOR and HIF-1 α related pathway proteins. Based on this, we propose a hypothesis that Xihuang Pill mediates PI3K/Akt/mTOR/HIF-1α signal axis to regulate PCa Warburg effect and promote vascular normalization. This project intends to explore the molecular mechanism and metabolic characteristics of Xihuang Pill in regulating PCa PI3K/Akt/mTOR/HIF-1α signal axis, blocking Warburg effect and promoting vascular normalization by using stable isotope tracer and metabonomics. The verification of this hypothesis will help to reveal the internal relationship between the metabolic changes of PCa and tumor progression, and provide a new vision and opportunity for the pathogenesis of castration resistant PCa.