扉页等单独打印.docx

单位代码10475学号104753111174分类号 R96硕士学位论文化合物T20对P-gp介导的K562/ADM细胞阿霉素耐药性的逆转作用学科、专业　：　药理学研究方向　　：　肿瘤药理申请学位类型：　医学硕士申请人　　　：　刘盟指导老师　　：　姬汴生教授二〇一四 年 六 月　 Reversal of resistance to adriamycin by Compound T20 in K562/ADM?cells?mediated by P-gpA Dissertation Submitted to the Graduate School of Henan Universityin Partial Fulfillment of the Requirementsfor the Degree ofMaster of MedicineBy: liumengSupervisor: Prof. Ji Biansheng 摘 要目的：探讨化合物T20对P-糖蛋白（P-glycoprotein，P-gp）介导的多药耐药肿瘤细胞K562/ADM细胞对阿霉素（adriamycin，ADM）多药耐药性的逆转作用。方法：通过高内涵活细胞成像系统测定K562和K562/ADM细胞内化合物T20对罗丹明123（Rh123）累积的影响；采用MTT法，测定化合物T20对K562和K562/ADM细胞的细胞毒作用，以及它对抗肿瘤药物ADM的耐药逆转作用；通过高内涵活细胞成像系统测定K562和K562/ADM细胞内化合物T20对ADM累积的影响；采用蛋白电泳（Western Bloting）测定化合物T20对K562/ADM细胞膜上P-gp表达的影响。结果：化合物T20可剂量依赖性的增加Rh123在K562/ADM细胞内的累积，对K562细胞无显著影响；化合物T20对K562和K562/ADM细胞的细胞存活率均无显著影响，可剂量相关性的增加对ADM的逆转倍数（reversal fold， RF），但对K562细胞无此作用；化合物T20可显著性的增加K562/ADM细胞内ADM的累积量，对K562细胞无显著影响；化合物T20在高浓度时使P-gp的表达明显减弱。结论：化合物T20可抑制K562/ADM细胞膜上P-gp的外排功能；化合物T20可增加抗肿瘤药物ADM对多药耐药细胞的细胞毒作用，具有多药耐药逆转活性；化合物T20能通过增加细胞内抗肿瘤药物ADM的浓度来逆转肿瘤细胞多药耐药 ；化合物T20具有多药耐药逆转活性，与降低K562/ADM细胞膜上P-糖蛋白的功能和表达有关。关键词：多药耐药，化合物T20，P-糖蛋白，MTT比色法，蛋白电泳ABSTRACTObjective:?To investigate the reversal of resistance to ADM by Compound T20 in K562/ADM cells mediated by P-gp.Methods: Effects of K562 and K562/ADM cells in compound T20 on Rh123 accumulation was measured by high?content of?live cell imaging?system; using MTT method, determination of cytotoxicity effect with compound T20 on K562 and K562/ADM cells, and its antineoplastic drug resistance reversal effect of ADM; To determine the effects of K562 and K562/ADM cells in compound T20 on ADM accumulation with high?content of live cell imaging system; Determination of the content of compound T20 on the expression of P-gp on the membrane of K562/ADM using Western Bloting.Results: Compound T20 could dose dependently increased Rh123 accumulation in K562/ADM cells had no significant effect on K562 cells. Compound T20 on?K562?and K562/ADM?cell survival rate?had no si