维甲酸与二甲基亚砜诱导HL-60细胞及其抗性亚型MDR 1的表达和对Rhodamine-123外排的影响

INDUCTION OF EXPRESSION OF MDR 1 GENE BY RETINOIC ACID AND DMSO AND EFFECTS ON RHODAMINE-123 EFFLUX IN HL-60 CELL LINES AND RESISTANT SUBLINES

摘要: 利用Dot blot 和流式细胞术，研究了分化诱导剂维甲酸，DMSO对HL-60细胞及其抗性亚型抗药性程度的影响，表明1μmol·ml^-1 RA 作用H-60及其亚型24h， MDR 1 mRNA 明显增高，但流式检测多药抗性细胞系对Rho-123的外排有所下降。2%DMSO作用HL-60及其亚型 24h，流式细胞术检测显示各细胞系对Rho-123 的外排明显增强，提示RA 虽然提高MDR 1基因的表达，但可能通过磷酸化/脱磷酸化方式抑制Pgp-170功能的表达，而DMSO能诱导完整功能的Pgp表达。

Abstract: Using dot blot hybridization and flowcytometry, the effects of differentiation inducers retinoic acid (RA) and dimethyl sulfoxide (DMSO) on the resistant level of HL-60 cells cells and its resistant subline cells were studied. When the cells were treated with RA 1μmol·ml^-1 for 24h, the expression of MDR 1 mRNA evidently increased in both HL-60 and its multidrug resistant subline cells. The efflux of Rho-123 in the multidrug resistant subline cells was slightly decreased. But, when the cells were treated with 2% DMSO for 24h the efflux of Rho-123 increased obviously. The results suggest that RA can induce the expression of MDR1 gene but perhaps inhibit the function of pump glycoprotein 170(Pgp-170) through phosphorylation/dephosphorylation pathway. However, DMSO could induce the expression of full function of Pgp.