AGEs与其受体相互作用与K562及K562/A02细胞耐药性

目的观察晚期糖基化终末产物(AGEs)与其受体相互作用是否与K562及K562/A02细胞对阿霉素(ADM)耐药性相关。方法用流式细胞术检测K562及K562/A02细胞晚期糖基化终末产物受体(RAGE)及P-糖蛋白(P-gp)的表达和细胞凋亡率,CCK-8法观察AGEs对K562及K562/A02细胞增殖的影响,计算AGEs作用下两种细胞对ADM的半抑制浓度(IC50)值,用半定量RT-PCR检测mdr1mRNA相对表达水平。结果 K562与K562/A02细胞RAGE表达比较差异无统计学意义。AGEs可呈浓度和依赖性促进K562及K562/A02细胞增殖(P<0.05);AGEs作用K562及K562/A02细胞48h后,K562细胞mdr1mRNA及P-gp的表达均为阴性,K562/A02细胞mdr1mRNA及P-gp的表达与不加AGEs组比较差异均无统计学意义。结论 AGEs不能改变K562细胞对ADM的敏感性,同时亦不能改变K562/A02细胞对ADM的耐药性;AGEs与其受体相互作用与K562及K562/A02细胞耐药性无关。

Relationship between AGEs-RAGE interaction and drug resistance of K562 and K562/A02 cells

Objective To investigate the relationship between interaction of advanced glycation end products(AGEs) and the receptor of AGE(RAGE) and adriamycin(ADM)-resistance of K562 and K562/A02 cells. Methods The expressions of RAGE in K562 and K562/A02 cells were detected by flow cytometer(FCM),the effects of AGEs on proliferation of K562 and K562/A02 cells and the concentration causing 50% inhibition of cell growth(IC50) of ADM for K562 and K562/A02 cells incubated with AGEs were determined by CCK-8 assay,the apoptosis rate and expression of P-glycoprotein(P-gp) in K562 and K562/A02 cells were detected by FCM,the expression of mdr1 mRNA was detected by semi-quantitative RT-PCR. Results There was no obvious change in the expression of RAGE between K562 and K562/A02 cells.The proliferation of K562 and K562/A02 cells was promoted by AGEs in concentration-and time-dependent manner.There was no significant difference in IC50 of ADM for K562 and K562/A02 cells between incubation with ADM alone and combined with AGEs for 24 h and 48 h.So did in the apoptosis of K562 and K562/A02 cells for 48 h.The expressions of mdr1 mRNA and P-gp of K562 cells incubated with AGEs for 48 h were all negative.There was no obvious change in the expressions of mdr1 mRNA and P-gp of K562/A02 cells incubated with or without AGEs for 48 h. Conclusion AGEs can not change the sensitivity of K562 cells and resistance to ADM of K562/A02 cells.AGEs-RAGE interaction is not related with drug resistance of K562 and K562/A02 cells.