二氟尼柳调控ILP-2/Bcl-2/Bax信号通路促进乳腺癌细胞凋亡  

Diflunisal Promotes Breast Cancer Cells Apoptosis by Regulating the ILP-2/Bcl-2/Bax Signaling Pathway

作　　者：彭航 向思琦 蒋双艳 崔如霞 向明钧[1] PENG Hang;XIANG Siqi;JIANG Shuangyan;CUI Ruxia;XIANG Mingjun(Department of Basic Medicine,Jishou University School of Medicine,the Key Laboratory of the State Ethnic Affairs Commission of XiangxiMiao Medicine,Pediatric Tuina Medical Intersection and Transformation,Jishou 416000,China)

机构地区：[1]吉首大学医学院基础医学系,湘西苗医小儿推拿医工交叉与转化国家民委重点实验室,吉首416000

出　　处：《中国细胞生物学学报》2023年第7期1038-1046,共9页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:81360397);湖南省教育厅科学研究项目(批准号:22A0354)资助的课题。

摘　　要：该文旨在探讨二氟尼柳对乳腺癌细胞MCF-7、MDA-MB-231凋亡的影响及分子机制。采用CCK-8法检测不同浓度二氟尼柳对乳腺癌细胞增殖的影响;平板克隆形成实验检测二氟尼柳对乳腺癌细胞克隆形成的作用;细胞划痕实验检测细胞的迁移情况;吖啶橙/溴化乙锭双荧光染色法(AO-EB)分析细胞凋亡情况;采用Western blot(WB)法检测ILP-2、Bax、Bcl-2、Cleavedcaspase-3的蛋白表达水平。结果显示,与对照组相比,二氟尼柳显著抑制MCF-7、MDA-MB-231细胞增殖,且抑制率与药物浓度和时间呈正相关;平板克隆形成率降低;药物显著抑制细胞的迁移能力;细胞凋亡的数量增加,凋亡率呈药物浓度依赖性趋势;Cleaved-caspase-3、促凋亡蛋白Bax表达量上调,凋亡抑制蛋白ILP-2及抗凋亡蛋白Bcl-2表达显著下调,且呈药物浓度依赖性。结果表明,二氟尼柳下调ILP-2蛋白表达影响Bcl-2/Bax信号通路从而促进乳腺癌细胞凋亡。This paper aimed to discuss the effects of diflunisal on the apoptosis of MCF-7 and MDAMB-231 breast cancer cells and its molecular mechanism.CCK-8 assay was applied to detect the effect of different concentrations of diflunisal on breast cancer cell proliferation.The effect of diffunisal on the clone formation of breast cancer cell was detected by plate clone formation.The migration of breast cancer cell was determined by the scratch assay.Apoptosis of breast cancer cell was analyzed by AO-EB(acridine orange/ethidium bromide).The protein expression levels of ILP-2,Bax,Bcl-2 and Cleaved-caspase-3 were detected by WB(Western blot).CCK-8 showed that compared with the control group,the diflunisal group significantly inhibited MCF-7 cells and MDAMB-231 cells,and the inhibition increased with concentration and time.Diflunisal significantly inhibited the migration ability of the cells.The number of apoptotic cells increased,and the apoptosis rate was drug concentrationdependent.Western blot showed upregulation of pro-apoptotic proteins Cleaved-caspase-3 and Bax,and significant downregulation of apoptosis inhibitor protein ILP-2 and anti-apoptotic protein Bcl-2.As the drug concentration increased,the expression level of each protein changed more significantly.Results indicate that diflunisal induces breast cancer cell apoptosis by downregulating ILP-2 protein expression and subsequently affecting the Bcl-2/Bax signaling pathway.

关 键 词：二氟尼柳 乳腺癌 ILP-2 BCL-2/BAX 凋亡 

分 类 号：R96[医药卫生—药理学]