硒化壳聚糖逆转K562/ADM细胞耐药与PI-3K/Akt信号通路的关系  

The correlation between of selenium chitosan and the reversal of drug resistance of K562/ADM cells and the PI-3K/Akt signaling pathway

作　　者：邓守恒[1] 潘东风[1] 李芳[1] 李林均[1] 王贤和[1] 陈萍[1] 

机构地区：[1]湖北医药学院附属人民医院肿瘤中心,湖北十堰442000

出　　处：《现代预防医学》2014年第2期286-289,共4页Modern Preventive Medicine

基　　金：湖北省自然科学基金(2008CDZ048);湖北医药学院基金(2008QDJ1)

摘　　要：目的研究硒化壳聚糖对体外培养多药耐药白血病细胞株K562/ADM的耐药逆转作用,探讨其与PI-3K/Akt信号通路的关系。方法 K562/ADM细胞培养于含0.6μg/ml阿霉素的培养液中维持其耐药性,应用MTT法检测硒化壳聚糖对K562/ADM细胞增殖的作用,计算逆转倍数;应用流式细胞法检测细胞凋亡;应用免疫印迹法检测磷酸化Akt(p-Akt)和P糖蛋白(P-gp)表达的改变。结果 K562/ADM细胞对阿霉素(ADM)耐药,硒化壳聚糖可有效抑制K562/ADM细胞增殖,呈一定的剂量和时间效应关系(P<0.05,P<0.01);硒化壳聚糖能够对K562/ADM细胞耐ADM产生一定的逆转作用,明显增强ADM对K562/ADM细胞的诱导凋亡作用(P<0.05,P<0.01),下调p-Akt和P-gp水平(P<0.01)。结论硒化壳聚糖对耐药白血病细胞株K562/ADM可产生增殖抑制和多药耐药逆转作用,其部分逆转机制可能是通过诱导细胞凋亡,抑制细胞P-gp表达,阻断细胞PI-3K/Akt信号通路而实现。Objective The study aimed to investigate the reversing effect of selenium chitosan on drug resistance of cultured mul- tidrug resistant leukemia cell lines K562/ADM cells and its correlation with the PI-3K/Akt signaling pathway. Methods K562/ADM cells were cultured in medium supplemented with 0.6 Ixg/ml of adriamycin to maintain their drug resistance. MTI7 method was adopted to measure the effect of selenium chitosan on the proliferation of K562/ADM cells and to calculate the multiplicity of the re- versal. Apoptosis of the cells was assessed by flow cytometry, and changes in the expression of phosphorylated Akt （p-Akt） and phosphorylated glycoprotein （P-gp） were determined by immunoblotting. Results K562/ADM cells were resistant against adriamycin （ADM）. Selenium chitosan could effectively inhibit the proliferation of K562/ADM cells in a dose- and time-dependent manner （P〈 0.05, P〈0.01）. Selenium chitosan could reverse the resistance of K562/ADM against ADM, significantly enhance the apoptosis of K562/ADM cells induced by ADM （P〈0.05, P〈0.01）, and downregnlate the expression of p-Akt and P-gp （P〈0.01）. Conclusion Selenium chitosan can inhibit proliferation and reverse muhidrug resistance of drug-resistant leukemia cell lines K562/ADM. The reversal of drug resistance may partially involve the induction of cell apoptosis, inhibition of cellular expression of P-gp, and block- age of the PI-3K/Akt signaling pathway.

关 键 词：硒化壳聚糖 多药耐药 信号通路 

分 类 号：R96[医药卫生—药理学]