特异性下调尿路上皮癌细胞HER-2表达增强表柔比星抗肿瘤效应的实验研究  

Experimental study on enhancing the anti-tumor effect of epirubicin by specifically down-regulating the expression of HER-2 in urothelial cancer cells

作　　者：章逸翔 卢童 王澍[1,2] 龚化 戴强[2] ZHANG Yixiang;LU Tong;WANG Shu;GONG Hua;DAI Qiang(Medical College,Wuhan University of Science and Technology,Hubei Wuhan 430065,China;Urology Surgery,the First People's Hospital of Tianmen City,Hubei Tianmen 431700,China)

机构地区：[1]武汉科技大学医学部医学院,湖北武汉430065 [2]天门市第一人民医院泌尿外科,湖北天门431700

出　　处：《现代肿瘤医学》2024年第17期3206-3212,共7页Journal of Modern Oncology

摘　　要：目的:观察在尿路上皮癌细胞内特异性下调人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER-2)表达对表柔比星(epirubicin,EPI)抗肿瘤效应的影响。方法:对比正常尿路上皮细胞系SV-HUC-1与3种尿路上皮癌细胞系T24、SW780、TCCSUP的HER-2蛋白表达差异,并筛选出其中HER-2表达较高的尿路上皮癌细胞T24与TCCSUP;设计针对HER-2基因的小干扰RNA-siHER-2,将其导入T24和TCCSUP细胞,观察siHER-2特异性下调T24和TCCSUP细胞HER-2表达的效率;随后将siHER-2和EPI共同导入T24和TCCSUP细胞,采用流式细胞术检测各组细胞凋亡水平的差异;并采用Western Blot检测各组细胞PI3K/AKT/mTOR凋亡信号通路相关蛋白表达水平。结果:3种尿路上皮癌细胞的HER-2表达均明显高于正常尿路上皮细胞(P<0.01);siHER-2可明显下调T24和TCCSUP细胞内HER-2表达量(P<0.01);siHER-2与EPI联合应用,可显著提高T24和TCCSUP细胞的凋亡率(P<0.001);同时两种细胞内p-PI3K/PI3K、p-AKT/AKT、p-mTOR/mTOR明显下调(P<0.001)。结论:特异性下调尿路上皮癌细胞内HER-2表达可有效增强EPI的抗肿瘤效应,可作为尿路上皮癌治疗的一种新型策略。Objective:To observe the effect of specific downregulation of human epidermal growth factor receptor-2(HER-2) expression in urothelial carcinoma cells on the antitumor effect of epirubicin(EPI).Methods:The HER-2 protein expression differences were compared between the normal urothelial cell line SV-HUC-1 and three urothelial carcinoma cell lines T24,SW780,and TCCSUP,and T24 and TCCSUP cells with higher HER-2 expression were screened out.Small interfering RNA(siRNA) targeting HER-2 gene(siHER-2) was designed and introduced into T24 and TCCSUP cells to observe the efficiency of HER-2 downregulation.Subsequently,siHER-2 and EPI were co-introduced into T24 and TCCSUP cells,and the differences in apoptotic levels of cells treated with siHER-2 and EPI alone and in combination were detected using flow cytometry.Western Blot was used to detect the expression levels of PI3K/AKT/mTOR apoptotic pathway-related proteins in each group of cells.Results:HER-2 expression in the three urothelial carcinoma cells was significantly higher than that in the normal urothelial cells(P<0.01).siHER-2 could significantly downregulate HER-2 expression in T24 and TCCSUP cells(P<0.01).The combination of siHER-2 and EPI could significantly increase the apoptotic rate of T24 and TCCSUP cells(P<0.001),while the p-PI3K/PI3K,p-AKT/AKT,and p-m TOR/m TOR levels in both cell types were significantly decreased( P < 0.001).Conclusion:Specific downregulation of HER-2 expression in urothelial carcinoma cells can effectively enhance the antitumor effect of EPI and may serve as a new strategy for the treatment of urothelial carcinoma.

关 键 词：HER-2 表柔比星 尿路上皮癌 凋亡 

分 类 号：R737.1[医药卫生—肿瘤]