摘要
目的探讨苦参素(oxymatrine,OM)及Mir-181a在体内环境中对人肝癌细胞耐药株HepG2/ADM裸鼠移植瘤中耐药蛋白P-糖蛋白(P-glycoprotein,P-gp)的影响。方法选用人肝癌细胞耐药株HepG2/ADM细胞在裸鼠腋下接种,创建裸鼠皮下移植瘤模型。将42只雌性裸鼠随机分成6组(每组7只):miR-181amimic组、苦参素组、苦参素+miR-181amimic组、阿霉素组、mirna mimic NC组、空白对照组。药物干预18d后,取出瘤体,用公式计算肿瘤体积。HE染色法观察组织的细胞病变情况,免疫组化及Western blot法检测耐药指标P-gp蛋白的表达,实时荧光定量PCR检测P-gp对应耐药基因ABCB1表达的情况。结果药物干预18d后,与空白对照组相比,miR-181amimic组的P-gp蛋白及ABCB1基因的表达提高,而苦参素组的P-gp蛋白及ABCB1基因的表达降低;与miR-181amimic组相比,苦参素+miR-181amimic组P-gp蛋白及ABCB1基因的表达降低。结论苦参素在体内环境中不仅可以抑制人肝癌耐药移植瘤的生长,还可提高人肝癌耐药细胞对化学药物的敏感性,而miR-181a在体内环境中可以促进人肝癌耐药移植瘤的生长,提高人肝癌耐药细胞的多药耐药性。
Objective To investigate the effect of oxymatrine and Mir-181 aon drug-resistant protein Pglycoprotein(P-gp)in nude mice with xenograft of human hepatocellular carcinoma drug resistant cell line HepG2/ADMin vivo. Methods HepG2/ADM cells of human hepatocellular carcinoma drug-resistant cells were inoculated in the axilla of nude mice to create a subcutaneous tumor xenograft model of nude mice.Fortytwo female nude mice were randomly divided into 6 groups(seven in each group):miR-181 amimic group,oxymatrine group,oxymatrine+miR-181 amimic group,adriamycin group,mirna mimic NC group,and blank control group.Eighteen days after drug intervention,the tumor was removed and the tumor volume was calculated using a formula.HE staining was used to observe the cytopathological changes of the tissues.Immunohistochemistry and Western blot methods were used to detect the expression of drug resistance index P-gp.Realtime fluorescent quantitative PCR was used to detect the expression of drug resistant gene ABCB1 corresponding to P-gp. Results Eighteen days after drug intervention,compared with the blank control group,the expressions of P-gp protein and ABCB1 gene in the miR-181 amimic group increased,while the expressions of Pgp protein and ABCB1 gene in the matrine group decreased;compared with miR-181 amimic group,the expressions of P-gp protein and ABCB1 gene in oxymatrine+miR-181 a mimic group was reduced. Conclusion Oxymatrine can not only inhibit the growth of tumors transplant by human liver drug resistant cancer cell in vivo,but also increase the sensitivity of human liver cancer drug resistant cells to chemical drugs,but miR-181 a can promote the growth of human liver cancer drug resistant xenograft tumors in vivo and improve the multidrug resistance of human liver cancer drug resistant cells.
作者
廖俊
张彩灵
黄赞松
覃小珊
陈椿
Liao Jun;Zhang Cailing;Huang Zansong;Qin Xiaoshan;Chen Chun(Graduate School of Youjiang Medical University for Nationalities,Baise 533000,Guangxi,China;Affiliated Hospital of Youjiang Medical University for Nationalities,Guangxi Clinical Medicine Center for Liver Disease,Baise 533000,Guangxi,China)
出处
《右江民族医学院学报》
2020年第1期1-6,共6页
Journal of Youjiang Medical University for Nationalities
基金
广西自然科学基金资助项目(桂财教2014GXNSFAA118143)
广西科技基地与人才专项(桂科AD17129025)
广西医药卫生自筹经费计划课题(桂卫Z20170224)
广西研究生教育创新计划项目(YCSW2019220)
