EGFR突变阳性非小细胞肺癌中上皮间质转化对EGCG逆转吉非替尼耐药的作用  

Role of epithelial-mesenchymal transition in reversing gefitinib resistance by EGCG in EGFR-mutation-positive non-small-cell lung cancer

作　　者：侯磊[1] 安改丽[1] 孙晶莹[2] 冯阳蒙 霍雪萍[2] 赵永丽 HOU Lei;AN Gaili;SUN Jingying;FENG Yangmeng;HUO Xueping;ZHAO Yongli(Department of Medical Oncology,Shaanxi Provincial People’s Hospital,Xi’an 710068,China;Department of Central Laboratory,Shaanxi Provincial People’s Hospital;Department of Operating Room,Shaanxi Provincial Kangfu Hospital)

机构地区：[1]陕西省人民医院肿瘤内科,西安710068 [2]陕西省人民医院中心实验室 [3]陕西省康复医院手术室

出　　处：《山西医科大学学报》2021年第7期812-817,共6页Journal of Shanxi Medical University

基　　金：陕西省自然科学基金面上项目(2017JM8106)。

摘　　要：目的探索表没食子儿茶素没食子酸酯(epigallocatechin-3-gallate,EGCG)在EGFR突变阳性非小细胞肺癌中逆转吉非替尼耐药与上皮间质转化(epithelia-mesenchymal transition,EMT)的作用。方法首先构建吉非替尼耐药的PC9细胞。将实验分为5组,分别为PC9耐药组、EGCG处理PC9耐药细胞的EGCG组、吉非替尼处理PC9耐药细胞的吉非替尼组、吉非替尼联合EGCG处理PC9耐药细胞的吉非替尼+EGCG组以及PC9组。MTT法检测细胞半数致死量(IC 50)。流式细胞仪检测细胞周期及凋亡变化。Western blot检测细胞Caspase-3、Bcl-2、E-cadherin与N-cadherin蛋白表达。结果与吉非替尼组比较,吉非替尼+EGCG组IC 50明显降低(P<0.05)。与PC9耐药组、吉非替尼组及EGCG组比较,吉非替尼+EGCG组细胞G2/M期增多(P<0.05),凋亡百分数增多(P<0.05)、Caspase-3表达增多(P<0.05),Bcl-2表达减少(P<0.05)。与PC9组比较,PC9耐药组细胞E-cadherin表达减少(P<0.05),N-cadhrein表达增多(P<0.05);与PC9耐药组比较,EGCG组细胞E-cadherin表达增多,N-cadhrein表达减少(P<0.05)。结论EGCG能够逆转吉非替尼耐药,其中对EMT抑制发挥了一定作用。Objective To explore the role of epigallocatechin-3-gallate(EGCG)on gefitinib resistance and epithelia-mesenchymal transition(EMT)in EGFR-mutation-positive non-small-cell lung cancer.Methods Gefitinib resistant PC9 cells were constructed.Then the experiment was divided into five groups:gefitinib resistant PC9 group,EGCG group(gefitinib resistant PC9 cells treated with EGCG),gefitinib group(gefitinib resistant PC9 cells treated with gefitinib),gefitinib+EGCG group(gefitinib resistant PC9 cells treated with gefitinib+EGCG)and PC9 group.IC 50 was analyzed by using MTT method.Cell cycle and apoptosis were detected by flow cytometry.The expression levels of Caspase-3,Bcl-2,E-cadherin and N-cadherin were detected by Western blot.Results Compared with gefitinib group,the IC 50 was decreased in gefitinib+EGCG group(P<0.05).Compared with gefitinib-resistant group,gefitinib group and EGCG group,the percentage of G2/M phase cells and the rate of apoptosis cells were increased in gefitinib+EGCG group(P<0.05),and the expression of Caspase-3 protein expression was increased(P<0.05),while Bcl-2 protein expression was decreased(P<0.05).Compared with PC9 group,the expression of E-cadherin protein was decreased in gefitinib-resistant group(P<0.05),N-cadhrein protein expression was increased(P<0.05).Compared with gefitinib-resistant group,the expression of E-cadherin protein was increased in EGCG group(P<0.05),while N-cadherin protein was decreased(P<0.05).Conclusion EGCG can reverse the gefitinib resistance,in which the inhibition of EMT plays an important role.

关 键 词：表没食子儿茶素没食子酸酯 上皮间质转化 吉非替尼 非小细胞肺癌 

分 类 号：R734.2[医药卫生—肿瘤]