基础医学与临床 ›› 2020, Vol. 40 ›› Issue (7): 934-939.

• 研究论文 • 上一篇    下一篇

雷帕霉素下调mTOR-GP73通路抑制结直肠癌进程

张梦迪, 王亚南, 李杰, 浦洋*   

  1. 中国医学科学院基础医学研究所 北京协和医学院基础学院 生理学系, 北京 100005
  • 收稿日期:2020-05-13 修回日期:2020-05-14 出版日期:2020-07-05 发布日期:2020-06-29
  • 通讯作者: *puyang_py@163.com
  • 基金资助:
    国家自然科学基金(81602456, 31700785)

Rapamycin inhibits colorectal cancer progression through down-regulating mTOR-GP73 pathway

ZHANG Meng-di, WANG Ya-nan, LI Jie, PU Yang*   

  1. Department of Physiology, Institute of Basic Medical Sciences CAMS, School of Basic Medicine PUMC, Beijing 100005, China
  • Received:2020-05-13 Revised:2020-05-14 Online:2020-07-05 Published:2020-06-29
  • Contact: *puyang_py@163.com

摘要: 目的 探讨高尔基蛋白(GP73)促进人结直肠癌细胞增殖的机制及其潜在调控。方法 应用GEPIA网站分析人结直肠癌样本的GP73基因表达。用慢病毒GV115载体系统构建GP73敲低的Caco2和HT-29细胞株。CCK8法和克隆形成实验检测GP73敲低对结肠癌细胞系增殖的影响。使用雷帕霉素处理结肠癌细胞系,CCK8法检测雷帕霉素对结肠癌细胞系增殖能力的影响;用蛋白免疫印记法检测STAT3信号通路传导情况。用雷帕霉素治疗野生型的AOM-DSS诱导的结直肠癌荷瘤(CAC)小鼠,蛋白质免疫印迹检测治疗后的小鼠mTOR通路激活情况和GP73蛋白水平。结果 GP73在人结直肠癌组织中高表达。GP73敲低抑制结直肠癌细胞系增殖。雷帕霉素可以通过下调GP73抑制AOM-DSS模型诱导的结直肠癌进展,GP73下调会导致结直肠癌细胞对雷帕霉素的治疗不敏感。结论 GP73在人结直肠癌组织中高表达,下调GP73抑制人结直肠癌细胞增殖。雷帕霉素通过下调mTOR-GP73通路抑制结直肠癌的进程。

关键词: 结直肠癌, mTOR, GP73

Abstract: Objective To explore the mechanism and potential regulation of GP73 in human colorectal cancer cell proliferation. Methods GEPIA website was used to analyze GP73 gene expression in human colorectal cancer samples. shRNA targeting GP73 was constructed and then transfected into Caco2 and HT-29 cells to knock-down GP73 expression. Cell proliferation was measured by CCK8 assay. Colony formation experiment was used to detect cell proliferation. CCK8 method was used to detect control cells and GP73-knockdown HT-29 cell proliferation after rapamycin treatment. Wild type mice administered with AOM-DSS induced colitis-associated colorectal cancer (CAC) were treated with rapamycin. Western blot was used to detect protein levels of mTOR and GP73 pathway in treated mice. Results GP73 is highly expressed in human colorectal cancer tissues. Deficient-GP73 inhibited human colorectal cancer cell proliferation. Rapamycin suppressed AOM-DSS induced CAC development and down regulated mTOR-GP73 axis. Down-regulation of GP73 caused human colorectal cancer cells insensitive to rapamycin treatment. Conclusions GP73 is highly expressed in human colorectal cancer tissues. Deficient-GP73 inhibits proliferation of human colorectal cancer cells. Rapamycin inhibits the progression of colorectal cancer through down-regulation of mTOR-GP73 pathway.

Key words: colorectal cancer, mTOR, GP73

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