乳腺癌前病变IL-6R/JAK2/STAT3信号通路调控血管生成的作用及乳岩内消霜外用干预机制

IL-6R/JAK2/STAT3信号通路是调控乳腺组织癌变过程中血管生成的核心机制，与乳腺组织癌变密切相关。前期研究证实乳岩内消霜外用对乳腺癌前病变有良好治疗作用，可显著下调癌前病变组织细胞IL-6R、p-STAT3、VEGF蛋白水平，抑制血管生成，提示其良好疗效与通过该信号通路调节乳腺癌前病变血管生成密切相关。本项目通过DMBA联合雌孕激素序贯诱导动物模型，采用免疫印迹、液质联用等技术，检测该信号通路与血管生成关键信号分子IL-6R、p-STAT3等变化水平，协同CAM血管生成、细胞划痕等实验，明晰该信号通路调控乳腺癌前病变血管生成的核心机制及介导乳岩内消霜通过该信号通路调节血管生成的关键信号分子，并利用MCF-10AT细胞模型，阻断或沉默关键信号分子进行确证。此研究可进一步揭示乳腺癌前病变发生发展的分子机制，及该霜有效外治乳腺癌前病变和预防、阻断乳腺癌发生发展的作用机理甚至作用靶点。

The signaling pathway of IL-6R/JAK2/STAT3 is the core mechanism in regulating angiogenesis during the carcinogenesis of breast, which indicates a close relation with breast cancer. Previous studies have confirmed that the external use of Ruyanneixiao Cream has an excellent therapeutic effect on breast precancerous lesions, which could significantly down-regulate IL-6R, p-STAT3, and VEGF protein levels and inhibit angiogenesis, suggesting that this beneficial effect of Ruyanneixiao Cream may be closely related to the regulation of angiogenesis in breast precancerous lesions through this signaling pathway. This project detects the key signaling molecules IL-6R, p-STAT3 levels of this signaling pathway and angiogenesis on animal models induced by DMBA combined with the sequential therapy of estrogen and progesterone by Western blot and LC-MS, etc, coordinating CAM angiogenesis and wound healing assay and other experiments, to clarify the core mechanisms that IL-6R/JAK2/STAT3 signaling pathway regulates angiogenesis in breast precancerous lesions and the key signaling molecules of the signaling pathway in regulating angiogenesis mediated by Ruyanneixiao Cream. And to confirm this mechanism by blocking or silencing the key signaling molecules in the MCF-10AT cell model. This study may further clarifies breast precancerous lesions pathogenesis and reveals the mechanism and even targets of Ruyanneixiao Cream for effective external treatment in breast precancerous lesions and preventing and blocking the development of breast cancer.