天然产物研究与开发 ›› 2023, Vol. 35 ›› Issue (1): 22-32.doi: 10.16333/j.1001-6880.2023.1.003

• 研究论文 • 上一篇    下一篇

基于Hippo信号通路的野黄芩苷抗结直肠癌HCT116细胞的研究

杨   寒，任   珊，刘茂伦，赵   晖，陶   秋，唐   顺，明天琪，徐海波*   

  1. 成都中医药大学药学院药理系 西南特色中药资源国家重点实验室，成都 611137
  • 出版日期:2023-01-28 发布日期:2023-02-20
  • 基金资助:
    国家自然科学基金面上项目（81573813）；四川省中医药管理局课题（2021XYCZ007，2021MS447）；四川省卫生健康委员会医学科技项目（21PJ107）

Suppression of colorectal cancer HCT116 cells by scutellarin via regulation of Hippo signaling pathway

YANG Han,REN San,LIU Mao-lun,ZHAO Hui,TAO Qiu,TANG Shun,MING Tian-qi,XU Hai-bo*   

  1. State Key Laboratory of Southwestern Chinese Medicine Resources,Department of Pharmacology,School of Pharmaceutical Sciences,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China
  • Online:2023-01-28 Published:2023-02-20

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摘要：

本文旨在探究野黄芩苷（scutellarin，SCU）对人结直肠癌HCT116细胞的作用及机制。不同浓度SCU处理人结直肠癌HCT116细胞，采用显微镜观察法、MTT法、平板克隆形成试验、细胞划痕试验、Hoechst 33342/PI双染法、流式细胞术、qRT-PCR以及Western blot等多种手段进行检测。结果显示，SCU能明显改变HCT116细胞形态，降低细胞活力；抑制HCT116细胞克隆和迁移（P<0.01）；诱导细胞核致密浓染，促进细胞凋亡，使细胞凋亡率显著增加（P<0.05或P<0.01）。机制研究结果表明，SCU能显著上调caspase-9、caspase-3的mRNA表达水平（P<0.01），下调Bcl-2的mRNA和蛋白表达水平（P<0.01），上调Bax的mRNA和蛋白表达水平（P<0.01）。此外，SCU能明显升高MST1、LATS1的mRNA和蛋白表达量（P<0.05或P<0.01），升高p-YAP(Ser127)的蛋白表达量（P<0.05或P<0.01），降低YAP1、TAZ和下游靶点c-Myc的mRNA和蛋白表达量（P<0.05或P<0.01）。综上所述，SCU能通过调节Hippo信号通路的活性，抑制HCT116细胞的增殖和迁移，并诱导细胞凋亡，从而发挥抗结直肠癌的作用。

关键词: 野黄芩苷, 结直肠癌, 增殖, 迁移, 凋亡, Hippo信号通路

Abstract:

To investigate the efficacy of scutellarin (SCU) on human colorectal cancer HCT116 cells and its underlying mechanism.Colorectal cancer HCT116 cells were treated with SCU at various concentrations,followed by measurement of cell proliferation with MTT assay,clonogenic assay,wound healing assay,Hoechst 33342/PI double staining,flow cytometry analysis of apoptosis,qRT-PCR and Western blotting.The results showed that SCU reduced the proliferation of HCT116 cells with altered morphological profile.SCU markedly deterred the colony formation and migration of HCT116 cells (P<0.01).Moreover,SCU triggered the apoptosis of HCT116 cells,with condensed nuclear staining and increased apoptosis rate,relative to the control (P<0.05 or P<0.01).Mechanistically,SCU significantly up-regulated the mRNA levels of caspase-9 and caspase-3 (P<0.01),promoted the mRNA and protein expression of Bax (P<0.01),and attenuated the mRNA and protein expression of Bcl-2 (P<0.01).In addition,the mRNA and protein expressions of MST1 and LATS1,and the protein level of p-YAP(Ser127) were elevated by SCU (P<0.05 or P<0.01),which lessened the mRNA and protein expressions of YAP1,TAZ and downstream target c-Myc in HCT116 cells (P<0.05 or P<0.01).Taken together,SCU may suppress the proliferation,migration and colony formation and induce cell apoptosis of colorectal cancer cells,by regulation of Hippo signaling pathway activity.

Key words: scutellarin, colorectal cancer, proliferation, migration, apoptosis, Hippo signaling pathway

中图分类号:  R285.5

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