摘要
本研究旨在探讨白血病耐药细胞的发生及其逆转机制与细胞内钙离子浓度的关系。用甲基四唑蓝法(MTT)测定柔红霉素 (daunomycin ,DNR)的细胞毒性 ,用Fura 2 /AM方法测定耐药细胞株K5 6 2 /A0 2及其敏感株K5 6 2的静息 [Ca2 +]i水平 ,并观察了柔红霉素及耐药调节剂汉防己甲素 (Tetrandrine,Tet)、屈洛昔芬 (droloxifene,DRL)单独或联合应用后细胞内游离钙离子浓度的变化。结果表明 :1μmol/LTet,5 μmol/LDRL均能增加DNR对耐药细胞系K5 6 2 /A0 2的细胞毒作用 ,IC50 (半数抑制量 )分别为 ( 7.2 8± 2 .0 6 ) μg/ml,( 7.5 8± 3.4 4 ) μg/ml,逆转倍数为 2 .94和 2 .82倍。两药联合作用明显增强 ,IC50 为 ( 1.6 6± 0 .4 1) μg/ml,逆转倍数达 12 .9倍。静息状态下K5 6 2 /A0 2细胞的游离钙离子浓度显著高于K5 6 2细胞。 1μmol/LTet,5 μmol/LDRL单独作用于K5 6 2 /A0 2细胞引起 [Ca2 +]i的明显升高 ,两者联合应用有拮抗作用。结论 :K5 6 2 /A0 2细胞内Ca2 +浓度的增高可能是导致其耐药的原因之一 ,但耐药调节剂Tet,DRL对耐药细胞 [Ca2
To explore the relationship of multidrug resistance formation in K562/A02 cells with the intracellular concentration of [Ca 2+ ]i, the cytotoxicities of daunorubicin (DNR) were assayed by MTT method, the variations of [Ca 2+ ]i of K562 cells and K562/A02 cells after treatment of Tet, DRL and DNR alone or in combination were detected by using Fura 2/AM. The results showed as follows: (1) The cytotoxicities of DNR to cell line K562/A02 were enhanced by 1 μmol/L Tet or 5 μmol/L DRL. Their IC 50 was (7.28±2.06)μg/ml and (7.58±3.44) μg/ml; multiple of their reversal effect was 2.94 and 2.82, but IC 50 of combined Tet and DRL was (1.66±0.41) μg/ml. Its reverse effect distinctly increased by 12.9 times. (2) The [Ca 2+ ]i in K562/A02 cells were higher than that in K562 cells. (3) One μmol/L Tet and 5 μmol/L DRL alone increased the [Ca 2+ ]i in K562/A02 cells time dependently and there was antagonism when both were used. It is concluded that high [Ca 2+ ]i is supposed to be a reason of MDR in K562/A02 cells, the action of resistance modifying agents (RMA) in MDR reverse course, however, needs further research.
出处
《中国实验血液学杂志》
CAS
CSCD
2004年第2期159-162,共4页
Journal of Experimental Hematology
基金
国家自然科学基金资助项目 编号 3 9970 83 2
