埃克替尼介导FXR受体通过下调miR-21水平抑制非小细胞肺癌细胞增殖及侵袭能力机制分析  

Mechanism of Icotinib-mediated FXR Receptor Inhibiting the Proliferation and Invasion of Non-small Cell Lung Cancer Cells by Down-regulating the Level of miR-21

作　　者：王立[1] 胡春秀[1] 姜忠于 刘学武[1] Wang Li;Hu Chunxiu;Jiang Zhongyu;Liu Xuewu(Department of Oncology,Zhejiang Quhua Hospital,Zhejiang Quzhou324004,China)

机构地区：[1]浙江衢化医院肿瘤科,浙江衡州324004

出　　处：《中国药师》2022年第7期1133-1137,共5页China Pharmacist

基　　金：衢州市科技项目(编号:2019ASA90038)。

摘　　要：目的:探讨埃克替尼介导FXR受体通过下调miR-21水平抑制非小细胞肺癌(NSCLC)细胞增殖及侵袭能力机制。方法:体外培养人肺癌A549细胞,分为对照组、A组(埃克替尼10μmol·L^(-1))、B组(埃克替尼20μmol·L^(-1))、C组(埃克替尼40μmol·L^(-1))、D组(埃克替尼80μmol·L^(-1))和E组(埃克替尼80μmol·L^(-1)+FXR抑制剂Z-guggulsterone)。取对数生长期细胞,根据相应方案进行转染处理,处理前、处理24,48,72 h时取细胞进行相关检测。采用实时PCR分析处理前后的miR-21和FXR的miRNA相对表达量。采用western blotting法检测FXR的蛋白表达水平。采用四甲基偶氮唑蓝(MTT)法检测细胞增殖抑制率。采用Transwell小室法进行细胞侵袭和迁移能力分析。结果:随着埃克替尼给药剂量的增加,FXR的miRNA相对表达量和蛋白表达水平以及miR-21的miRNA相对表达量降低,细胞增殖抑制率升高,细胞迁移和侵袭数减少(P<0.05)。与E组比较,D组FXR的miRNA相对表达量和蛋白表达水平以及miR-21的miRNA相对表达量升高,细胞增殖抑制率降低,细胞迁移和侵袭数增加(P<0.05)。随着处理时间的延长,各组FXR的miRNA相对表达量和蛋白表达水以及miR-21的miRNA相对表达量均降低,细胞增殖抑制率升高,细胞迁移和侵袭数减少(P<0.05)。结论:埃克替尼可抑制NSCLC细胞增殖及侵袭,埃克替尼介导FXR受体下调miR-21表达可能为其作用机制。Objective:To investigate the mechanism of icotinib-mediated FXR receptor inhibiting the proliferation and invasion of non-small cell lung cancer(NSCLC)cells by down-regulating the level of miR-21.Methods:Human lung cancer A549 cells were cultured in vitro and divided into control group(0μmol·L^(-1) icotinib),group A(10μmol·L^(-1) icotinib),group B(20μmol·L^(-1) icotinib),Group C(40μmol·L^(-1) icotinib),group D(80μmol·L^(-1) icotinib)and group E(80μmol·L^(-1) icotinib+FXR inhibitor Z-guggulsterone).The cells in the logarithmic growth phase were transfected according to the corresponding protocol.The cells were taken for relevant testing before treatment and after 24 h,48 and 72 h treatment.The miRNA relative expression levels of miR-21 and FXR before and after processing were analyzed by real-time PCR.Western blotting was used to detect the protein expression level of FXR.Tetramethylazazole blue(MTT)method was used to detect the inhibition rate of cell proliferation.Transwell cell method was used to analyze cell invasion and migration capability.Results:Compared to those in the control group,the relative expression of miRNA,the protein expression of FXR and the relative expression of miRNA of miR-21 decreased,the inhibition rate of cell proliferation increased,and the number of cell migration and invasion decreased in group A,group B,group C and group D with the dose increase of icotinib(P<0.05).Compared with those of group E,the relative expression of miRNA and protein expression and the relative expression of miRNA of miR-21 increased,the inhibition rate of cell proliferation decreased,and the number of cell migration and invasion increased in group D(P<0.05).With the extension of the treatment time,the relative expression of miRNA and protein expression level of FXR and the relative expression of miRNA of miR-21 in each group decreased,the inhibition rate of cell proliferation in each group increased,and the number of cell migration and invasion in each group decreased(P<0.05).Conclusion:Icotinib ca

关 键 词：埃克替尼 FXR受体 MIR-21 非小细胞肺癌 细胞增殖 侵袭 

分 类 号：R965.1[医药卫生—药理学]