高压氧联合阿霉素对白血病K562/A02细胞凋亡的影响  

Effects of Hyperbaric Oxygen Combined with Adriamycin in Inducing Apoptosis of K562/A02 Cells

作　　者：张伟[1] 陈宝安[2] 鲍文[2] 程坚[2] 孙燕[1] 成杰[1] 张敏[1] 张晓敏[1] 陈岩[1] 

机构地区：[1]东南大学医学院病理生理系,江苏南京210009 [2]东南大学医学院附属中大医院血液科,江苏南京210009

出　　处：《中国实验血液学杂志》2011年第3期621-625,共5页Journal of Experimental Hematology

基　　金：国家自然科学基金(编号30872970);国家大学生创新性实验计划(编号081028645)

摘　　要：本研究探讨0.2MPa高压氧(HBO)联合阿霉素对白血病多药耐药细胞K562/A02细胞凋亡的影响。利用流式细胞术法和透射电子显微镜检测细胞凋亡和caspase-3表达,用定量qReal-time PCR法检测HIF-1α、BCL-2和BAXmRNA表达水平,运用caspase-8试剂盒检测caspase-8的活性,Western blot法检测P-gp活性。结果表明:0.2MPa HBO联合阿霉素组细胞凋亡率高于ADM组[(47.36±3.87)%vs(28.51±1.09)%],差异有统计学意义(p<0.05)。0.2MPa HBO联合阿霉素组细胞HIF-1αmRNA、P-gp及BCL-2的蛋白水平低于ADM组,差异有统计学意义(p<0.05)。0.2MPa HBO联合阿霉素组细胞的BAX、caspase-3及caspase-8蛋白活性均高于ADM组,差异有统计学意义(p<0.05)。结论 :0.2MPa HBO联合阿霉素可逆转耐药细胞株K562/A02对阿霉素的耐药,提高细胞凋亡率,其机制可能与HIF-1α下调P-gp和BCL-2的表达以及提高caspase活性有关。This study was purposed to explore the effects of hyperbaric oxygen （HBO） combined with adriamycin （ADM） on inducing apoptosis of multidrug resistant cells line K562/A02. The cell apoptosis and expression of caspase- 3 activity were analyzed by flow cytometry and transmission electron microscopy; the expression levels of HIF-1 α, BCL- 2 and BAX mRNA were detected by quantitative real time PCR; the caspase 8 activity was determined by using caspase 8 kit; the expression level of P-gp was detected by Western blot. The results showed that the apoptosis rate of K562/A02 cells in combination group （0.2 MPa HBO ＋ ADM） was higher than that in ADM group [ （47.36 ±3.87） % vs （28.51 ± 1.09） % ], the difference was statistical significant （p 〈 0.05） ; the expression levels of HIF-let mRNA, P- gp and BCL-2 in combination group were lower than those in ADM group, there were significant differences （p 〈 0.05） ; the activities of BAX, caspase 3 and caspase 8 proteins in combination group were higher than those in ADM group, the difference was statistical significant （p 〈 0.05）. It is concluded that 0.2 MPa HBO combined with ADM can reverse the drug-resistance of K562/A02 cells to ADM, enhance the apoptosis rate of cells. The molecular mechanism may be related with downregulation of P-gp and BCL-2 expression, and up-regulation of caspase-3 and caspase-8 activities by HIF-1α.

关 键 词：高压氧 阿霉素 K562/A02细胞 多药耐药 细胞凋亡相关蛋白 

分 类 号：R733.7[医药卫生—肿瘤] R979.1[医药卫生—临床医学]