小鼠腹水型肝癌多药耐药模型的建立  

Establishment of Hca multidrug resistance mouse model

作　　者：王欣[1,2] 张艳[1] 王宁[1] 江金花[1] 郑立运[1] 王庆端[1] 

机构地区：[1]郑州大学医药科学研究院、河南省肝病药理重点实验室,郑州 450052 [2]河南省食品药品检验所,郑州 450052

出　　处：《郑州大学学报（医学版）》2010年第6期920-923,共4页Journal of Zhengzhou University(Medical Sciences)

基　　金：河南省杰出人才创新基金资助项目0521002200

摘　　要：目的:建立小鼠腹水型肝癌(Hca)多药耐药(MDR)模型并探讨其产生的分子机制。方法:荷Hca小鼠分为2组,每组10只。化疗组采用临床化疗FAP方案,以剂量递增的方法诱导耐药模型,对照组仅给予等体积的生理盐水。MTT法检测瘤细胞对7种化疗药物的耐药性;流式细胞术检测瘤细胞对Rh123的蓄积与泵出能力,计算平均荧光强度(MFI);RT-PCR检测瘤细胞mdr1和mrp1mRNA的表达及停药后化疗组小鼠瘤细胞mdr1和mrp1mR-NA的表达。结果:化疗组小鼠瘤细胞对7种化疗药物均产生耐药性。与对照组相比,化疗组小鼠瘤细胞内Rh123蓄积量减少,泵出率增加(t=6.067和6.811,P均<0.05),mdr1和mrp1mRNA的表达水平升高(t=18.807和4.420,P均<0.05);mdr1和mrp1mRNA的表达水平在停药4周内稳定(P>0.05),停药8周后下降(P<0.05)。结论:成功建立了小鼠腹水型肝癌MDR模型,MDR的产生与mdr1和mrp1mRNA过度表达从而影响药物蓄积有关。Aim：To establish a multidrug resistance（MDR） model of ascites type hepatocellular carcinoma（Hca） in mouse and discuss its molecular mechanism.Methods：Twenty mice were randomly divided into chemotherapy group and control group with 10 mice in each group.The chemotherapy group was continuously exposured to increasing doses of drugs to acquire MDR using FAP chemotherapy regimen.The control group was given normal saline.Resistance indexes of seven chemotherapy drugs were measured by MTT assay.Accumulation and efflux activities of rhodamine 123 in the tumor cells were determined by flow cytometry.The mdr1 and mrp1 mRNA expression level in tumor cells was measured using RT-PCR.Results：The tumor cells in the chemotherapy group developed drug resistance to seven cytotoxic agents.Compared with control group,decreased drug accumulation and increased efflux were found（t=6.067 and 6.811,P0.05）,and the mdr1 and mrp1 mRNA levels were increased significantly in the tumor cells of the chemotherapy group （t=18.807 and 4.420,P0.05）.mdr1 and mrp1 mRNA levels after drug absence for 4 weeks had no significant difference from 0 week（P0.05）.Conclusion：MDR model of ascites type Hca in mice has been established successfully, and the possible molecular mechanism may be that overexpression of mdr1 and mrp1 mRNA influences the drug accumulation.

关 键 词：肝细胞癌 FAP方案 多药耐药 小鼠 

分 类 号：R-332[医药卫生]