Puerarin逆转K562/AO2耐药的分子机制  

Molecular mechanism of reversing multi-drug resistance of K562/AO2 by puerarin

作　　者：陈进伟[1] 陶师[1] 骆蓉[1] 张广森[1] 徐运孝[1] 

机构地区：[1]中南大学湘雅二医院血液科,长沙410007

出　　处：《中南大学学报（医学版）》2008年第3期216-221,共6页Journal of Central South University ：Medical Science

基　　金：湖南省科学技术厅科技计划资助项目(05SSY3069)~~

摘　　要：目的:研究黄酮类化合物puerarin对K562/AO2(人红白血病多药耐药细胞系)细胞耐药逆转作用的分子机制。方法:免疫荧光染色方法检测阿霉素(ADR)和puerarin对K562(人红白血病细胞系)和K562/AO2两种细胞NF-κB活性的影响;免疫细胞化学染色方法检测ADR和puerarin对K562和K562/AO2的survivin表达的影响;流式细胞仪检测ADR和puerarin对K562和K562/AO2的p-gp表达的影响。结果:经ADR处理后的K562细胞和K562/AO2细胞NF-κB的活性明显高于K562细胞空白对照组;经puerarin预处理后再加ADR处理的K562细胞中的NF-κB的活性明显低于只用ADR处理的K562细胞。经puerarin干预后的K562/AO2细胞的NF-κB的活性明显低于未经puerarin干预的K562/AO2细胞;经ADR处理后的K562细胞和K562/AO2细胞的p-gp,survivin表达明显高于K562细胞空白对照组;经puerarin预处理后再加ADR处理的K562细胞中的p-gp,survivin表达明显低于未经pu-erarin预处理的K562细胞;经puerarin干预后的K562/AO2细胞的p-gp,survivin表达明显低于未经puer-arin干预的K562/AO2细胞。p-gp和survivin表达呈正相关。结论:NF-κB的活化使p-gp和survivin表达增多可能是K562细胞多药耐药形成的机制之一。Puerarin能预防和阻止K562细胞耐药形成,并能逆转K562/AO2对ADR的耐药,其机制与抑制NF-κB活性及survivin和p-gp的表达有关。Objective To determine the molecular mechanism of reversing multi-drug resistance of K562/AO2 by puerarin. Methods Effects of ADR and puerarin on NF-KB activity of K562, K562/AO2 were tested by immunoflurescence. The expression of survivin of K562, K562/ AO2 was examined by immunocytochemistry. The p-gp expression was detected by flow cytometry. Results The NF-KB activity of K562 was significantly higher than that of K562/AO2. The NF-KB activity of K562 treated by ADR was significantly higher than untreated. The NF-KB activity of K562 which was pretreated by puerarin and then treated by ADR was much lower than that treated by ADR alone. The NF-KB activity of K562/AO2 intervened by puerarin was lower than that unintervened by puerarin. The p-gp and survivin expression of K562/AO2 was significantly higher than K562. The p-gp and survivin expression of K562 treated by ADR was higher than that untreated by ADR. But the p-gp and survivin expression of K562 which was pretreated by puerarin and then treated by ADR was much lower than that not pretreated by puerarin. The p-gp and survivin expression of K562/AO2 intervened by puerarin was lower than that unintervened by puerarin. The expression was negatively correlated to the duration of intervention. The inhibition effect demonstrated time dependence. Conclusion The activation of NF-KB can increase the expression of p-gp and survivin, which may be part of the molecular mechanism of multi-drug resistance of K562. Puerarin can prevent and stop the multi-drug resistance in K562 and reverse the multi-drug resistance of K562/AO2 to ADR by inhibiting the activity of NF-KB and the expression of p-gp and survivin.

关 键 词：PUERARIN K562/A02 药耐药 逆转 分子机制 

分 类 号：R733.7[医药卫生—肿瘤]