miRNA介导中药对胃癌细胞增殖和凋亡调控作用的研究

MiRNAs have been identified as oncogenes or tumor suppressors, and they have been regarded as potential drug targets. However, there are no reports on miRNAs-mediated gastric cancer therapies of Chinese Medcine. In this study, we aim to detect the efffect of Yangzheng Sanjie Decoction containing serum on miRNA expression profiles in different gastric cancer cell lines using miRNA chip technology, screen and verify the differentially expressed miRNAs related to proliferation and apoptosis combined with the application of bioinformatics method and real-time quantitative PCR technology; to observe the change of proliferation and apoptosis of gastric cancer cells in vitro through antagonism to drug containing serum by mimics or inhibitors transfection; and to examine the percentage of tumorigenesis and the tumor volume, detect miRNA expression, proliferation index and apoptosis index in tumor tissues from nude mouse models of human gastric cancer by Yangzheng Sanjie Decoction intragastric administration. Above all, this study aims to explore the miRNAs-mediated regulative effects of Yangzheng Sanjie Decoction on proliferation and apoptosis of gastric cancer and lay a foundation for further research on molecular biological mechanism of gastric cancer therapies of Chinese Medcine.

miRNA在肿瘤发生发展过程中起着重要作用，是抗癌治疗潜在的药物靶点。本课题拟在前期研究基础上，采用miRNA芯片进一步检测养正散结汤含药血清对胃癌细胞miRNA表达谱的影响，结合生物信息学方法，筛选并验证可能与增殖凋亡有关的miRNA；转染miRNA拟似物或抑制剂拮抗中药的干预作用，验证中药发挥作用的miRNA途径；寻找并鉴定介导中药作用的miRNA靶基因；构建胃癌荷瘤鼠模型，观察中药对成瘤能力的影响，检测肿瘤组织中miRNA表达及增殖和凋亡指数；进行体内miRNA功能获得实验及功能缺失实验，验证miRNA是否具有介导中药发挥作用的功能。通过上述实验，探讨中药复方对胃癌miRNA表达的调控及中药抗增殖、促凋亡的miRNA新途径，为进一步阐明中药复方治疗胃癌的分子机制，发挥中药治疗胃癌的优势，奠定新的理论基础。

近年来，越来越多的研究证实miRNA在胃癌发生发展过程中起着重要作用。本课题在前期研究基础上，采用miRNA芯片进一步检测养正散结汤含药血清对胃癌细胞miRNA表达谱的影响，结合生物信息学方法，筛选并验证了与增殖凋亡有关的miR-7、Let-7；寻找并鉴定了介导中药作用的miRNA靶基因；构建胃癌荷瘤鼠模型，观察中药对移植瘤生长的影响，检测肿瘤组织中miRNA表达及增殖指数；并检测了人胃癌组织、癌旁组织及远处胃黏膜组织miR-7、Let-7a及靶基因的表达。通过本项目研究，证实了中药复方养正散结汤具有调控胃癌miRNA表达及抗增殖、促凋亡的作用，发现了介导养正散结汤发挥抗癌作用的miRNA及其靶基因，探讨了中药复方养正散结汤治疗胃癌的分子机制，为发挥中药治疗胃癌的优势提供了科学依据。