环孢菌素A雷洛昔芬及其联合应用逆转K562A02细胞多药耐药的研究.docVIP

环孢菌素A雷洛昔芬及其联合应用逆转K562A02细胞多药耐药的研究 目录 TOC \o 1-9 \h \z \u 目录 1 正文 1 文1：环孢菌素A雷洛昔芬及其联合应用逆转K562A02细胞多药耐药的研究 1 文2：环孢菌素A汉防己甲素及两者联合逆转K562A02细胞的多药耐药 9 1 材料和方法 10 2 结　　果 12 3 讨　　论 13 参考文摘引言： 14 原创性声明（模板） 15 文章致谢（模板） 16 正文 环孢菌素A雷洛昔芬及其联合应用逆转K562A02细胞多药耐药的研究 文1：环孢菌素A雷洛昔芬及其联合应用逆转K562A02细胞多药耐药的研究 Effect of Cyclosporine A, Raloxifene and Their Combination on the Reveion of Multidrug Resistace of K562/A02 Line AbstractThis study was aimed to investigate the reveible effect of cyclosporine A, raloxifene and their combination on multidrug resistance cell line K562/A02. The IC50 (the concentration causing 50% inhibition of cell growth) of DNR were assayed by MTT method, the expression level of mdr-1 mRNA was assayed by RT-PCR, p-glycoprotein (P-gp) expression and intracellular DNR concentration were detected by flow cytometry. The results showed that the IC50 of DNR on K562/A02 and K562 cells were mg/L and mg/L, respectively. The IC50 of DNR on K562/A02 cells in treatment with raloxifene CsA and both combination were , and mg/L respectively, but both drugs not influenced IC50 of DNR on K562 cells. Pretreating K562/A02 cells with raloxifene ( mg/L) or CsA (1 mg/L) for 48 hou partially restored the seitivity of K562/A02 cells to DNR. Cyclosporine A and raloxifene (alone or combination) elevated the intracellular DNR concentration in K562/A02, down regulated P-gp and mdr-1 mRNA expressio. It is concluded that multidrug resistance (MDR) can be partially reveed by CsA or raloxifene, the combination of both drugs shows a great synergistic reveal effect. Key wordscyclosporine A; estrogen-receptor inhibitor; raloxifene; K562/A02; drug resistance 多药耐药(multidrug resistance, MDR)系多因素所致,肿瘤细胞mdr1基因过度表达导致细胞膜上相对分子质量170×103的糖蛋白(P-glycoprotein, P-gp)增多是产生MDR的主要机制,P-gp具有药物泵的功能,能将进入肿瘤细胞内的化疗药物主动地泵出细胞外以减少细胞内药物蓄积,从而使肿瘤细胞发生MDR ［1］。肿瘤化疗失败的主要原因之一是多药耐药性的产生，因此如何成功地逆转多药耐药是当前肿瘤 治疗 学中的一个研究热点。已有 文献 报道，屈洛昔芬不能明显增强化疗药物柔红霉素（DNR）对K562敏感细胞的杀伤作用,但能明显增强DNR对K562/A02耐药细胞的杀伤作用［2］。国外有文献报道,单独应