8-溴-7-甲氧基白杨素抑制小细胞肺癌细胞上皮-间充质转化作用及其机制探讨  

8-bromo-7-methoxychrysin inhibits epithelial-mesenchymal transition and its mechanism

作　　者：唐甜[1] 安东建[2] 曹建国[3] 胡锦跃[4] 

机构地区：[1]南华大学肿瘤研究所,湖南衡阳421001 [2]长沙市中心医院肿瘤研究所,长沙410004 [3]湖南师范大学医学院药物工程实验室,长沙410013 [4]长沙市中心医院医学研究中心,长沙410004

出　　处：《中南药学》2017年第3期272-276,共5页Central South Pharmacy

基　　金：国家自然科学基金(No.81172375)

摘　　要：目的探讨8-溴-7-甲氧基白杨素(Br MCh R)抑制人小细胞肺癌细胞(NCI-H446细胞)中上皮-间充质转化(EMT)的作用机制,为寻找特异性阻断人小细胞肺癌的新型靶向治疗药物提供实验依据。方法 (1)体外培养NCI-H446细胞,倒置相差显微镜观察NCI-H446细胞形态;(2)细胞因子IL-6(0、0.5、1.0、5.0、10、20 ng·m L^(-1))诱导NCI-H446细胞发生EMT改变;(3)Western blot检测不同浓度Br MCh R(0、0.5、1.0、5.0μmol·m L^(-1))对STAT3、p-STAT3、E-cadherin、N-cadherin蛋白表达。结果(1)IL-6诱导NCI-H446细胞发生EMT,形成伪足,从椭圆形或圆形上皮细胞形态转变成梭形、多边形。p-STAT3蛋白表达升高、E-cadherin蛋白表达降低、N-cadherin蛋白表达增高。(2)Br MCh R降低STAT3、p-STAT3、N-cadherin蛋白表达,升高E-cadherin蛋白表达。结论 Br MCh R能通过抑制IL-6/STAT3信号通路阻断EMT发生,其作用机制可能与降低STAT3、p-STAT3、N-cadherin蛋白表达、升高E-cadherin蛋白表达有关。Objective To investigate the inhibition of epithelial-mesenchymal transition in human small cell lung cancer（NCI-H446） cell line induced by Br MCh R and its mechanism. And to seek new targeted drugs for specific block of small cell lung cancer. Methods（1） NCI-H446 cells was cultivated in vitro. The morphology of NCI-H446 cells was observed with inverted phase contrast microscope.（2） Cytokines IL-6（0, 0.5, 1.0, 5.0, 10 and 20 ng·m L^-1） induced EMT change in NCI-H446 cells.（3） The effect of different concentrations of Br MCh R（0, 0.5, 1.0 and 5.0 μmol · m L^-1） on STAT3, p-STAT3, E-cadherin, and N-cadherin protein expression was determined by Western blot. Results（1） IL-6 induced EMT in NCI-H446 cells, and pseudopodia was performed, from oval or round epithelial cells into spindle or polygons. The expression of p-STAT3 and Ncadherin was up-regulated by IL-6, but it induced the decrease of E-cadherin protein expression.（2） Br MCh R down-regulated the expression of STAT3, p-STAT3 and N-cadherin, but the expression of E-cadherin was upregulated by Br MCh R. Conclusion Br MCh R can inhibit IL-6/STAT3 signaling pathway to block the occurence of EMT in NCI-H446 cells, which may be due to the down-regulation of STAT3, p-STAT3, N-cadherin expression and the up-regulation of E-cadherin expression.

关 键 词：8-溴-7-甲氧基白杨素 IL-6/STAT3信号通路 上皮-间充质转化 小细胞肺癌 

分 类 号：R285[医药卫生—中药学]