孤啡肽逆转人白血病K562/ADM细胞耐药性的研究

目的 探讨孤啡肽对人白血病K562/ADM细胞对阿霉素耐药性的逆转作用.方法 测定孤啡肽的细胞毒性及其对K562/ADM细胞药物敏感性的影响,计算耐药逆转倍数.瑞士染色观察药物作用后K562/ADM细胞形态的改变;流式细胞仪检测阿霉素单用或与孤啡肽联用K562/ADM细胞凋亡百分率;DNA琼脂糖凝胶电泳观察孤啡肽与阿霉素联用后K562/ADM细胞内DNA的损伤程度.结果 非细胞毒性剂量的孤啡肽(10-7mol/L)作用于K562/ADM细胞时,对阿霉素耐药起到了部分逆转作用,使K562/ADM细胞的IC50由原来的(46.99±0.25)μg/ml降低至(23.11±0.29)μg/ml,其逆转倍数为2.03倍;孤啡肽(10-7mol/L)和阿霉素(20μg/ml)联合处理K562/ADM细胞48h,K562/ADM细胞呈典型的凋亡形态改变;细胞的凋亡率达到(18.73±3.90)%,明显高于两种药物在相同条件下单独作用的效果,P＜0.01;结论 孤啡肽能诱导K562/ADM细胞凋亡,从而能逆转K562/ADM细胞的耐药性,提高阿霉素的敏感性.

Studies of Nociceptin/orphanin FQ on reversal of Multidrug Resistant Leukemia Cell line (K562/ADM)

Objective To study the reversal effect of adriamycin(ADM) resistance by orphanin FQ(OFQ) in leukemia multi-drug resistance K562/ADM cells. Methods Cytotoxicity of OFQ and the sensibility to adriamycin of K562/ADM cells were studied through MTT assay. Morphological assessment of apoptosis was performed with light microscope after Wright staining and transmission electron microscope(TEM) . DNA Fragmentation was assessed by agarose gel electrophoresis. Results When the concentration of OFQ was 10-7mol/l,OFQ has no toxicity to K562/ADM cells. We found that OFQ could reverse the ADM resistance of K562/ADM cells. By the treatment of OFQ(10-7mol/l) ,K562/ADM cell were cultured for 48 hours,the reversal index(RI) was 2.03.Furthermore,it showed that OFQ could significantly increase apoptotic per-centage in K562/ADM cells. Conclusion OFQ can reverse multi-drug resistance in K562/ADM cells to some extent,they have distinctly synergy with ADM.