基于H-Ras/ERK/DRP1信号通路探讨桑根酮C靶向Galectin-1抑制胃癌细胞生长的分子机制研究

胃癌的临床治疗面临着巨大挑战，基于中药化合物的抗胃癌药物筛选为我们提供了研究策略。我们前期从中药单体化合物库中筛选出显著抑制胃癌细胞活力的桑根酮C，并通过蛋白质组学、生物信息学和药物亲和反应靶标稳定性等技术和方法，发现桑根酮C可能通过靶向Galectin-1，下调H-Ras/ERK/DRP1通路，抑制线粒体分裂，进而抑制胃癌细胞的生长。为了进一步验证这一结论，一方面通过体内实验构建裸鼠胃癌移植瘤模型，系统评价桑根酮C的体内抗肿瘤活性；另一方面，通过pull down、IP等实验探究桑根酮C靶向Galectin-1，破坏其与H-Ras的结合，进而通过下调ERK/DRP1通路，抑制线粒体分裂调控胃癌细胞生长的分子机制。该研究将为胃癌的药物研究提供新的作用靶点和研究思路。

The clinical treatment of gastric cancer meets tremendous challenges. The drug screening of anti-gastric cancer based on traditional Chinese medicine compounds provides us with research strategies. In our previous study, Sanggenon C was screened from the Traditional Chinese Medicine monomer library due to its significant inhibition in the viability of gastric cancer cells. It was found that Sanggenon C might inhibit the growth of gastric cancer cells by targeting Galectin-1 to down-regulate H-Ras/ERK/DRP1 pathway and to further inhibit mitochondrial division through proteomics, bioinformatics and DARTS technologies. To verify this hypothesis, on the one hand, the xenograft tumor model in nude mice were performed to systematically evaluate the antitumor activity of Sanggenon C in vivo. On the other hand, the experiments such as pull down and IP were committed to explore the molecular mechanism of Sanggenon C in inhibiting mitochondrial division to regulate the growth of gastric cancer cells by targeting Galectin-1 to destroy its binding with H-Ras and then down-regulating ERK/DRP1 pathway. This study will provide new targets and research ideas for drug research of gastric cancer.