高良姜素对缺氧诱导因子-1α诱导胃癌细胞上皮间质转化的作用机制  

Effect of galangin on hypoxia-inducible factor-1α-mediated epithelial mesenchymal transformation in gastric cancer cells

作　　者：贺文煜[1] 张海明 余涛[1] 李丹[2] HE Wen-yu;ZHANG Hai-ming;YU Tao;LI Dan(Dept of Integrated Traditional Chinese and Western Medicine,the Central Hospital of Wuhan,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430014,China;Dept of Pharmacy,Renmin Hospital of Wuhan University,Wuhan 430060,China)

机构地区：[1]华中科技大学同济医学院附属武汉中心医院中西医结合肿瘤科,湖北武汉430014 [2]武汉大学人民医院药学部,湖北武汉430060

出　　处：《中国药理学通报》2023年第5期839-843,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81704023);武汉市卫生健康委医学科研项目(No WZ20C27)。

摘　　要：目的探讨高良姜素(galangin,GLA)对缺氧微环境下胃癌的作用研究。方法采用CoCl_(2)诱导胃癌SGC-7901细胞株,体外模拟缺氧肿瘤微环境。使用CCK-8试剂,检测细胞活性;通过Transwell实验分析癌细胞侵袭能力;并通过蛋白印迹和逆转录PCR检测相关基因表达水平。结果研究显示,低中高浓度的GLA(50、100、150μmol·L^(-1))呈剂量依赖性抑制CoCl_(2)诱导胃癌SGC-7901细胞活性;且此浓度梯度对CoCl_(2)干预后的细胞侵袭也呈现明显抑制作用(P<0.01);深入研究发现,随着GLA浓度的提高,CoCl_(2)诱导引起的HIF-1α蛋白水平的升高被抑制,而HIF-1αmRNA水平未受影响;同时,上皮间质转化相关基因Snail和Vimentin的表达随GLA剂量增加而明显增加(P<0.05),而E-cadherin表达明显下降(P<0.01)。结论GLA能抑制肿瘤缺氧状态下的HIF-1α表达和上皮间质转化,从而抑制胃癌发展。Aim To investigate the effect of galangin(GLA)on gastric cancer in hypoxic microenvironment.Methods The gastric cancer SGC-7901 cell line was induced with CoCl_(2)to mimic the hypoxic tumor microenvironment in vitro.Cell viability assay was performed using CCK-8 reagent.The invasive ability of cancer cells was analyzed by Transwell assay.And the expression levels of relevant genes were detected by Western blotting and RT-qPCR.Results The study showed that low,medium and high concentrations of GLA(50,100 and 150μmol·L^(-1))presented a dose-dependent inhibition of CoCl_(2)-induced gastric cancer SGC-7901 cell viability.This concentration gradient also showed significant inhibition on cell invasion after CoCl_(2)intervention(P<0.01).In-depth study revealed that the CoCl_(2)-induced increased HIF-1αprotein expression was inhibited with increasing GLA concentration,while HIF-1αmRNA expression was not affected.Meanwhile,Snail and Vimentin expression of epithelial mesenchymal transition-related genes significantly increased with increasing GLA dose(P<0.05),whereas E-cadherin expression significantly decreased(P<0.01).Conclusions GLA inhibits HIF-1αexpression and epithelial mesenchymal transition under tumor hypoxia,thereby suppressing gastric cancer development.

关 键 词：高良姜素 胃癌 缺氧诱导因子-1Α 上皮间质转化 侵袭 缺氧微环境 

分 类 号：R284.1[医药卫生—中药学] R341[医药卫生—中医学] R341.31R394R735.2R845.22