中国药物警戒 ›› 2020, Vol. 17 ›› Issue (11): 758-765.
DOI: 10.19803/j.1672-8629.2020.11.03

• 基础与临床研究 • 上一篇    下一篇

染料木素促Bhas42细胞增殖及转化机制研究

汪祺1, 齐乃松2, 刘倩1, 宋捷1, 鄂蕊1, 马双成1,*, 文海若1,*   

  1. 1中国食品药品检定研究院,北京 100050;
    2河南省食品药品检验所,河南 郑州 450003
  • 收稿日期:2020-11-10 修回日期:2020-11-10 出版日期:2020-11-15 发布日期:2020-11-10
  • 通讯作者: *文海若,女,博士,研究员,药理毒理,E-mail:wenhairuo@nifdc.org.cn;马双成,男,博士,研究员,中药毒理,E-mail:msc@nifdc.org.cn
  • 作者简介:汪祺,女,副研究员,中药毒理。
  • 基金资助:
    国家自然科学基金(81503347,81503068); 国家“十三五重大新药创制”专项(2018ZX09201017-001)

Mechanisms of Genistein for Promoting Bhas42 Cell Proliferation and Transformation

WANG Qi1, QI Naisong2, LIU Qian1, SONG Jie1, AO Rui1, MA Shuangcheng1,*, WEN Hairuo1,*   

  1. 1National Institutes for Food and Drug Control, Beijing 100050, China;
    2Henan Provincial Institute of Food and Drug Control, Zhengzhou Henan 450003, China
  • Received:2020-11-10 Revised:2020-11-10 Online:2020-11-15 Published:2020-11-10

摘要: 目的 前期有关研究发现染料木素(genistein,GI)在一定条件下可促进Bhas42细胞转化,本文进一步研究GI促进细胞增殖及转化的潜在作用机制。方法 使用Bhas42细胞,检测GI在可导致细胞转化的浓度下(0.1、0.5、1 μg/mL)对细胞周期、细胞凋亡、细胞毒性(ROS、内质网功能、脂蓄积、线粒体膜电位、细胞内钙离子浓度)、氧化应激相关指标(SOD、MDA、GSH、8-HdG和ODC)、干扰细胞间隙连接通讯(gap junctional intercellular communication,GJIC)相关mRNA (PKC、Cx26、Cx32和Cx43)表达水平及肿瘤相关细胞因子表达水平(1L-6、KC/CXCL1、MCP-1、VEGF-A、VEGF-C、TNF-α、1L-1β、L-17A、VEGF-D)的影响。结果 GI可干预细胞周期调控,促进细胞增殖与转化(ODC水平升高、VEGF-A水平升高),并干扰GJIC功能,而氧化应激不是GI导致Bhas42细胞增殖或转化的重要机制。结论 本研究初步发现细胞周期调控通路和GJIC可能为黄酮类化合物促进细胞增殖及转化的主要作用机制。

关键词: 染料木素, 细胞增殖, 细胞转化, 细胞周期, 氧化应激, 细胞因子

Abstract: Objective To investigate the potential mechanism by which GI promotes cell proliferation and transformation. Methods Bhas42 cells were used to determine the effects of GI at concentrations that could lead to cell transformation (0.1、0.5 and 1μg/mL) on cell cycle, apoptosis, and cytotoxicities (ROS, endoplasmic reticulum function, lipid accumulation, mitochondrial membrane potential, intracellular calcium ion concentration), oxidative stress related indicators (SOD, MDA, GSH, 8-HdG and ODC), expression levels of GJIC related mRNAs (PKC, Cx26, Cx32 and Cx43 ) and expression levels of tumor-related cytokines (1L-6, KC/CXCL1, MCP-1, VEGF-A, VEGF-C, TNF-α, 1L-1β, L-17A, VEGF-D). Results GI could intervene in cell cycle regulation, promote cell proliferation and transformation, and disrupt the function of GJIC. However, oxidative stress is not an important mechanism by which GI causes the proliferation or transformation of Bhas42 cells. Conclusion This study indicates that the cell cycle regulation pathway and GJIC could be the main mechanisms by which GI promotes cell proliferation and transformation.

Key words: genistein, cell proliferation, cell transformation, cell cycle, oxidative stress, cytokine

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