uPAR衍生RERF肽逆转K562/ADM耐药及其机制  

Effect and mechanism of uPAR-derived peptide in reversing multi-drug resistance in human leukemia K562/ADM cells

作　　者：郭鸿[1] 张淑玲 周兰霞[3] 马云云 贾芳 胡新新[3] 张慧[3] 赵丽[3] 

机构地区：[1]兰州大学第一医院重症医学科,兰州730000 [2]兰州大学第一医院血液科,兰州730000 [3]兰州大学第一医院中心实验室,兰州730000

出　　处：《兰州大学学报（医学版）》2018年第1期59-64,共6页Journal of Lanzhou University（Medical Sciences）

基　　金：甘肃省卫生行业项目(GWGL2013-23)

摘　　要：目的采用新合成的尿激酶型纤溶酶原激活物受体(uPAR)衍生肽(RERF肽),探讨其对白血病耐药细胞K562/ADM耐药性的逆转作用及其机制。方法应用MTT法观察RERF肽对K562/ADM细胞生长增殖影响及非细胞毒素剂量对耐药逆转作用。应用实时荧光定量PCR(qPCR)检测RERF肽作用后K562/ADM细胞中uPA、uPAR和MDR1基因的表达;Western blot检测RERF肽作用后K562/ADM细胞中uPA、uPAR和P-gp蛋白的表达。结果 ADM单独作用K562/ADM细胞24、48、72 h,IC50分别为92.48±0.27、30.99±0.19、28.06±0.12μg/m L;ADM与非细胞毒性剂量的RERF肽共同作用K562/ADM细胞24、48、72 h,IC50分别降低为83.83±0.29、18.52±0.17、16.38±0.13μg/m L。联合用药48 h后K562/ADM细胞其uPA、uPAR、MDR1 m RNA与uPA、uPAR和p-gp蛋白的表达量明显降低(P<0.05)。结论 RERF肽可部分逆转K562/ADM细胞对ADM的耐药性,提高ADM的敏感性。RERF肽有可能通过uPA/uPAR途径下调MDR1基因,降低P-gp的表达,从而逆转白血病耐药。Objective To investigate its effect of the newly synthesized uPAR-derived peptide （RERF peptide） on leukemic K562/ADM and its mechanism. Methods The effect of RERF peptide on the proliferation of K562/ADM cells was observed by MTT assay. The reversal effect of non-cytotoxic dose of RERF peptide on drug resistance of adriamycin resistant K562/ADM cells was observed. The relative expression of uPA, uPAR and MDR1 gene in K562/ADM cells was detected by qPCR. And the expression of uPA, uPAR and P-gp protein in K562/ADM cells were detected by a western blot analysis. Results The 1C5o values of K562/ADM cells were 92.48±0.27, 30.99±0.19,28.06±0.12 μg/mL respectively at 24 h, 48 h, and 72 h after ADM admin-istration. The ICso decreased to 83.83±0.29, 18.52±0.17, 16.38±0.13 μg/mL respectively at 24 h, 48 h and 72 h after ADM combined with non-cytotoxic doses of RERF peptide. The expression of uPA, uPAR, MDR1 mRNA and p-gp protein in K562/ADM cells after treatment 48 h were significantly decreased （P 〈 0.05）. Conclusion RERF peptide could partially reverse the drug resistance of ADM in K562/ADM cells and improve the sensitivity of ADM. RERF peptide could reverse the resistance by affecting MDR1 gene via the uPA/uPAR pathway and decrease the express of P-gp.

关 键 词：尿激酶型纤溶酶原激活物受体 RERF肽 多药耐药 

分 类 号：R453.9[医药卫生—治疗学]