乌梅丸调控肺转移微环境核心信号转导分子干预乳腺癌转移的研究

The improvement of malignant tumor clinical curative effect of traditional Chinese medicine also stay in the innovation of the formulas. Wumei wan in malignant tumor already had obtained the clinical curative effect,but Wumei wan intervention mechanism of malignant tumor research is very weak, unable to effectively promote the further development of clinical application. Tumor microenvironment include the tumor cells, immune cells, secretory cells factors ,and so on. There has a direct relationship on the growth and metastasis of malignant tumor. Adjusting the internal environment (including the tumor microenvironment) disorder, rather than directly killing tumor,has become an important field of traditional Chinese medicine.Wumei wan is given priority to with plum,Acid, sweet, bitter, xin as an organic whole.It’s effet is not in Qingrejiedu, phlegm fights, activating blood and remove stasis, but adjusting Cold and heat, Yin and Yang, vital qi and pathogens.The correlation of the whole regulation mechanism of Wumei wan and the regulating tumor microenvironment is the focus of this study.. Project observes the curative effect of Wumei wan intervention in breast cancer by bioluminescent living imaging techniques firstly. Then gene expression profile chip technology is applied to screen drugs for gene expression of the tumor metastasis microenvironment. Bioinformatics method is used to analyze and build signal transduction network, and to validate the network core molecular targets.Study can clarify biological basis of controlling breast tumor microenvironment about Wumei wan of Jue Yin disease. Study will help to push the Wumei wan for application in the clinical treatment of cancer, provide a new train of thought for Chinese medicine clinical treatment of tumor.

经典名方乌梅丸在癌症中已取得临床疗效，但其生物学机制尚未清楚，制约了临床的进一步应用。肿瘤微环境是指肿瘤细胞所处的由各种细胞、细胞因子等组成的局部环境，与肿瘤的生长转移有直接关系，涉及复杂的信号转导通路。调整内环境（含肿瘤微环境）紊乱，而非直接杀灭肿瘤细胞是中医药防治癌症的特点。乌梅丸集酸、甘、苦、辛为一体，不以清热解毒、化痰散结、活血祛瘀等祛邪功效为主，而以寒热、阴阳、邪正共调为功效特点。乌梅丸论治癌症的整体调理机制与调控肿瘤微环境的相关性即是本研究的关注点。. 首先以生物发光活体成像技术观察乌梅丸干预乳腺癌的整体疗效，然后应用基因表达谱芯片技术筛选药物对肿瘤肺转移微环境内基因表达的影响，以生物信息学方法构建差异基因涉及的信号转导网络，通过对网络中核心调控分子进一步分析获得目标作用靶群，从这一层面阐明乌梅丸调控乳腺癌肺转移微环境的生物学机制。项目为乌梅丸在中医肿瘤临床的运用提供了依据。

中医经典名方乌梅丸在癌症中已取得临床疗效，但其生物学机制尚未清楚，制约了临床的进一步应用。肿瘤微环境是指肿瘤细胞所处的由各种细胞、细胞因子等组成的局部环境，与肿瘤的生长转移有直接关系，涉及复杂的信号转导通路。调整内环境（含肿瘤微环境）紊乱，而非直接杀灭肿瘤细胞是中医药防治癌症的特点。乌梅丸集酸、甘、苦、辛为一体，不以清热解毒、化痰散结、活血祛瘀等祛邪功效为主，而以寒热、阴阳、邪正共调为功效特点。. 乌梅丸论治癌症的整体调理机制与调控肿瘤微环境的相关性即是本研究的关注点。首先以生物发光活体成像技术观察乌梅丸干预乳腺癌的整体疗效，然后应用基因表达谱芯片技术筛选药物对肿瘤肺转移微环境内基因表达的影响，以生物信息学方法构建差异基因涉及的信号转导网络，以及网络中核心调控分子，从这一层面阐明乌梅丸调控乳腺癌肺转移微环境的生物学机制。. 本研究结果显示乌梅丸可以一定程度上抑制小鼠乳腺原位接种的4T1细胞的生长和肺转移。进一步研究发现乌梅丸对肺转移微环境基因的影响主要涉及Circadian rhythm（昼夜节律），Protein processing in endoplasmic reticulum（内质网的蛋白质处理）, Chemokine signaling pathway（趋化因子信号通路） 和IL-17 signaling pathway（IL-17信号通路）等信号通路，且对其5个核心信号基因AGT、CCL20、CXCL9、CXCL10和HTR1B的表达有确切影响。. 本研究有利于揭示乌梅丸调控乳腺癌肺转移微环境的生物学基础，有助于推动乌梅丸在恶性肿瘤中的临床应用。