摘要
目的探讨苦参素(oxymatrine,OM)是否能通过调控多药耐药相关蛋白1(multidrug resistance-associated protein1,MRP1)表达提高多柔比星(doxorubicin,DOX)对人肝癌耐药裸鼠移植瘤的抑制作用。方法选用人肝癌多柔比星耐药HepG2/ADM细胞在裸鼠腋下接种,创建裸鼠皮下移植瘤模型。将20只雌性裸鼠随机分成4组:NS组(对照组)、OM组(苦参素组)、DOX组(多柔比星组)、OM+DOX组(多柔比星+苦参素组)。药物使用14d后,取出瘤体,用公式计算肿瘤体积,RT-PCR法检测MRP1之mRNA表达,免疫组化法检测MRP1之蛋白表达,各组进行对比。结果药物使用14d后,与NS组相比,OM+DOX组出现MRP1 mRNA与蛋白表达降低(P<0.05),抑瘤作用最佳。与NS组相比,OM组也出现MRP1 mRNA与蛋白表达降低(P<0.05),抑瘤效果仅次于联合组。然而,与NS组相比,DOX组的MRP1 mRNA与蛋白表达上调(P<0.05),对移植瘤的抑制效果较差,二者体积对比差异无统计学意义(P>0.05)。结论苦参素能通过调控MRP1 mRNA及蛋白表达,从而提高多柔比星对人肝癌耐药裸鼠移植瘤的抑瘤作用。
Objective To explore whether oxymatrine can enhance the inhibitory effect of doxorubicin(DOX)on human drug-resistant hepatocellular carcinoma xenograft in nude mice via regulating MRP1 expression. Methods The subaxillary skins of nude mice were subcutaneously inoculated with human adriamycin-resistant hepatocellular carcinoma strains HepG2/ADM cells to establish subcutaneously tumor xenograft models in nude mice.Twenty female nude mice were randomly allocated to 4 groups:normal saline control group(NS group),doxorubicin group(DOX group),oxymatrine group(OM group),doxorubicin+oxymatrine group(OM+DOX group).After the use of the drugs for 14 days,the tumor bodies were taken out.The formula method was applied to caculate the tumor volumes,RT-PCR assay was applied to detect MRP1 mRNA levels,and immunohistochemical method was used to measure the protein expressions of MRP1.The obtained measurements were compared among the four groups. Results After the use of the drugs for 14 days,the MRP1 mRNA and protein expressions in the OM+DOX group were lower than those in the NS group(P<0.05);the OM+DOX group had the strongest inhibitory effect on tumor xenografts in the four groups.The mRNA and protein expressions in the OM group were lower than those in the NS group(P<0.05);the OM group had the inhibitory effect on tumor xenografts that was second only to the OM+DOX group.Nevertheless,the mRNA and protein expressions in the DOX group were higher than those in the NS group(P<0.05).Comparison of tumor xenografts’volumes between the two groups showed that there was no statistically significant difference(P>0.05),so the DOX group had weaker inhibitory effect on tumor xenografts. Conclusion Oxymatrine can enhance the inhibitory effect of doxorubicin on human drug-resistant hepatocellular carcinoma xenograft in nude mice via regulating MRP1 mRNA and protein expression.
作者
冯巍巍
黎梨
黄赞松
邓志华
邓凤莲
廖俊
杨哲
李建基
Feng Weiwei;Li Li;Huang Zansong;Deng Zhihua;Deng Fenglian;Liao Jun;Yang Zhe;Li Jianji(Graduate School of Youjiang Medical University for Nationalities,Baise 533000,Guangxi;Guangxi Clinical Medical Research Center for Liver and Gallbladder Diseases,Affiliated Hospital of Youjiang Medical University for Nationalities,Baise 533000,Guangxi)
出处
《右江民族医学院学报》
2018年第1期8-12,共5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(广西肝胆疾病临床医学研究中心研究课题)(桂科AD17129035)
2017年度广西医药卫生自筹经费计划课题(桂卫Z20170224)
2017年广西研究生教育创新计划项目(桂学位YCSW2017214)
2016年广西研究生教育创新计划项目(桂学位YCSW 201601004)
广西高校右江流域特色民族医药研究重点实验室开放课题(kfkt2016025)
关键词
苦参素
多柔比星
肝肿瘤
移植
异种
小鼠
裸
MRP1
抗药性
肿瘤
oxymatrine
doxorubicin
liver neoplasms
transplantation,heterologous
mice,nude
MRP1
drug resistance,neoplasm
