苦参素通过调控ABCG2表达提高阿霉素抗人肝癌耐药裸鼠移植瘤的疗效

Oxymatrine can enhance the efficacy of adriamycin on human drug-resistant hepatocellular carcinoma xenograft tumor in nude mice via regulating ABCG2 expression

目的探讨苦参素能否通过调控ABCG2表达提高阿霉素抗人肝癌耐药裸鼠移植瘤的疗效。方法裸鼠腋下接种肝癌HepG2阿霉素耐药细胞(HepG2/ADM),构建移植瘤模型。将20只雌性裸鼠随机分成对照组、阿霉素组、苦参素组、联合组(阿霉素联合苦参素)。干预14d后,取出瘤体,HE染色法观察瘤组织细胞的形态,RT-PCR测ABCG2的mRNA水平,免疫组化及ELISA法测ABCG2蛋白水平,并对组间数据进行对比。结果干预14d后,与对照组相比,阿霉素组抗移植瘤作用不明显,且ABCG2mRNA和蛋白表达水平均升高(P <0.05),其他两组有促移植瘤坏死作用,并能降低ABCG2mRNA和蛋白表达(P <0.05)。与单独苦参素组相比,联合给药组促移植瘤坏死效果更好。结论苦参素能通过调控ABCG2mRNA与蛋白表达,从而提高阿霉素抗人肝癌耐药裸鼠移植瘤的疗效。

Objective To explore whether oxymatrine can enhance therapeutic effects of adriamycin on human drug-resistant hepatocellular carcinoma xenograft tumor in nude mice via regulating the expression of ABCG2. Methods Nude mice were subaxillaryinoculated with HepG2/human adriamycin-resistant hepatocellular carcinoma cells(HepG2/ADM)under armpit)to establish a model of xenograft tumor.Twenty female nude mice were randomly divided into control group,adriamycin group,oxymatrine group,and combined drug group(adriamycin combined with oxymatrine).After 14 days of intervention,the tumor body was removed and the tissue morphology was observed by HE staining.The ABCG2 mRNA expressions were determined by RT-PCR,ABCG2 protein expression was determined by immunohistochemistry and ELISA,and the data were compared among the four groups. Results After 14 days of intervention,compared with the control group,adriamycin group had no significant anti-graft tumor effect,and ABCG2 mRNA and protein expressions were increased(P <0.05),the other two groups could enhance graft tumor necrosis and reduce the expressions of ABCG2 mRNA and protein(P <0.05).Compared with the oxymatrine group,the combined drug group had better effect on promoting xenograft tumor necrosis(P <0.05). Conclusion Oxymatrine can enhance the efficacy of adriamycin on human drug-resistant hepatocellular carcinoma xenograft tumor in nude mice via regulating ABCG2 mRNA and protein expression.