西安交通大学学报(医学版)2013,Vol.34Issue(3):302-307,6.
白血病多药耐药裸鼠荷瘤模型的建立
Establishment of xenograft leukemia model with stable multidrug resistance in nude mice
摘要
Abstract
Objective To establish the xenograft leukemia model with stable multidrug resistance (MDR) in nude mice induced by low-dose repeated injection of Adriamycin. Methods The nude mice inoculated by K562 cells were injected with Adriamycin of low dosage. The growth curve of the nude mice was drawn during Adriamycin injection. The effects of Adriamycin on K562 cells were assessed by MTT assay. The expression of P-glycoprotein (P-gp) was determined by flow cytometry. The effect of Adriamycin on P-gp activity was evaluated by measuring intracellular Adriamycin accumulation. The expressions of P-gp, MDR-associated protein (MRP1) and lung resistance-related protein (LRP1) genes were detected by fluorescence quantitative polymerase chain reaction. The expressions of P-gp, MRP1 and LRP1 were measured by immunohistochemistry. Results All nude mice were successfully inoculated and tumors were induced. Compared with that in the control group, IC50 of the cell line to the various chemotherapeutic agents was increased after 8 weeks of Adriamycin injection. The expressions of MDR, MRP1 and LRP1 mRNA of the xenografts were higher than those in the control group. The immunohistochemistry results showed that the expressions of P-gp, MRP1 and LRP1 proteins were higher than those in the control group. The number of cells in synthetic phase was greater than that in the control group. The intracellular concentration of Adriamycin was obviously lower than that in the control group. Conclusion We successfully established the multidrug resistant animal model, which establishes groundwork for research on acquired multidrug resistance in tumor.关键词
移植瘤/白血病/多药耐药/K562/MDR1/MRP1/LRP1/P-gpKey words
xenograft/ leukemia/ multidrug resistance/ K562/ MDR1/ MRP1/ LRP1/ P-gp分类
医药卫生引用本文复制引用
曹渊,惠璐璐,秦蓉,方悦,许文林,沈慧玲..白血病多药耐药裸鼠荷瘤模型的建立[J].西安交通大学学报(医学版),2013,34(3):302-307,6.基金项目
国家自然科学基金资助项目(No.81070423 ()
No.81101677) ()
江苏省自然科学基金资助项目(No.BK2010332) (No.BK2010332)