解毒散结方调控VEGF信号通路抑制血管新生抗胃癌复发转移的研究

The invasion and metastasis of gastric cancer is the main cause of death, and angiogenesis plays a key role in the invasion and metastasis of cancer cells. In recent years, with the continuous research and in-depth excavation of traditional Chinese medicine, traditional Chinese medicine treatment has become an important means of anti tumor invasion and metastasis. The results of animal experiments showed that the effect of Jiedu Sanjie Recipe on tumor invasion and metastasis was not obvious. Therefore, in order to evaluate the therapeutic effect of Jiedu Sanjie Recipe on tumor invasion and metastasis and angiogenesis, the inhibition of angiogenesis was used as the breakthrough point in the transgenic zebrafish model and the endothelial cell model in vitro. At the same time, the VEGF pathway as a starting point, using the method of Western blot and Real-time PCR, and the regulation mechanism in zebrafish model of endothelial cell model were studied jiedusanjietang Decoction on anti angiogenesis effect, so as to clear the jiedusanjietang Decoction on tumor invasion and metastasis targets, provide the basis for its clinical application and research support further development.

胃癌的侵袭转移是导致患者死亡的主要原因，血管新生在癌细胞的侵袭转移过程中起着关键的作用。近年来，随着中医药不断的研究和深入挖掘，中医药治疗成为抗肿瘤侵袭转移的重要手段。前期动物实验结果表明，解毒散结方抗肿瘤侵袭转移疗效确切，然而其作用机制尚不完全清楚。因此，本研究以抑制血管新生为切入点，在体内转基因斑马鱼模型和体外内皮细胞模型上，评价解毒散结方抗肿瘤侵袭转移和血管新生的疗效。同时，以VEGF信号通路为切入点，用Western blot和Real-time PCR的方法，在内皮细胞模型和斑马鱼模型上分别研究解毒散结方抗血管新生作用的调控机制，从而明确解毒散结方抗肿瘤侵袭转移作用靶点，为其临床应用和进一步开发提供基础研究支持。

恶性肿瘤严重危害人类健康，其中胃癌在我国的发病率逐年攀升，中医药已经成为抗胃癌过程中不可或缺的重要组成部分，然而其关键作用环节和分子作用机制尚不完全清楚。本项目以侵袭转移的关键环节—VEGF信号通路介导的血管新生为切入点，在斑马鱼和人脐静脉内皮细胞模型上，体内外相结合研究解毒散结方抑制血管新生抗胃癌的作用。在人脐静脉内皮细胞模型上，解毒散结方显著抑制细胞的增殖、迁移、小管形成；解毒散结方显著激活MEK、ERK的磷酸化，抑制ERK、cRaf的蛋白表达，对MEK、VEGFR1、HIF蛋白表达没有影响。在斑马鱼胃癌移植瘤模型上，解毒散结方显著减少肿瘤的大小。解毒散结方可能调控VEGF及其受体kdr、kdrl的mRNA表达抑制血管新生抗胃癌侵袭和转移。解毒散结方的有效成分可能是橙皮苷、迷迭香酸、华蟾酥毒基、脂蟾毒配基、重楼皂苷Ⅰ、重楼皂苷Ⅱ。本项目对解毒散结方的临床应用提供基础研究支持，同时对中医药治疗胃癌具有重要的意义。