【摘要】 目的:建立一种耐药性稳定的人绒毛膜癌裸鼠皮下移植瘤模型JAR/VP16/nude,为研究体内肿瘤耐药机制和逆转药物的筛选奠定实验基础。方法:将人绒毛膜癌多药耐药细胞系JAR/VP16接种于裸鼠左侧腋窝皮下,观察成瘤情况及肿瘤生长特性;利用光镜、电镜对移植瘤进行组织学和超微结构观察;逆转录-聚合酶链反应(RT-PCR)检测多药耐药基因mdr1 mRNA的表达;流式细胞术(FCM)分析细胞内罗丹明123(Rhodamine123,Rh123)的潴留情况。结果:裸鼠移植瘤模型构建成功率为98.39%,8~10d开始成瘤,15~20d瘤体长径达1.0~1.5cm;H-E染色及透射电镜观察发现瘤组织形态及细胞超微结构与人绒毛膜癌耐药细胞JAR/VP16相似;RT-PCR和FCM检测表明移植瘤组织mdr1 mRNA表达阳性,且对Rh123有显著的外排作用。结论:以JAR/VP16细胞建立的耐药性绒毛膜癌裸鼠移植瘤模型,保持了耐药性人绒毛膜癌细胞JAR/VP16的组织学特征和多药耐药性,为耐药性人绒毛膜癌耐药机制和逆转的研究提供了理想的动物模型。更多还原

【Abstract】 Objective: To establish a multidrug resistant (MDR) model of human choriocarcinoma using nude mice [BALB/c(nu/nu)], so as to provide evidence for studying MDR mechanism and for screening of the reversal drugs in vivo.Methods: MDR human choriocarcinoma JAR/VP16 cells of tumors were subcutaneously injected into the left armpit of nude mice. The tumor forming in mice and growth characteristics of tumors were observed. The morphologic characteristics of tumors were observed under light and transmission electron-microscope. Mdr1 mRNA expression and intracellular rhodamine123 (Rh123) retention were determined by RT-PCR and FCM, respectively.Results: Successful tumor forming was achieved in 98.39% of animals. Tumors began to form on 8-10 days and their diameter reached 1.0-1.5 cm on 15-20 days. H-E staining and transmission electron microscope revealed that the formed tumors had the same morphological characteristics as parent JAR/VP16 cells. Meanwhile, the tumor cells in nude mice expressed high level of mdr1 mRNA and had reduced Rh123 retention compared with JAR cells.Conclusion: The subcutaneous xenograft model in nude mice has the morphological and biological characteristics of multidrug resistant human choriocarcinoma, which paves a way for studying the mechanism of MDR human choriocarcunoma and for studying the reversal of MDR.更多还原