摘要
目的 :研究氧化砷 (三氧化二砷 ,As2 O3 )对肿瘤耐药蛋白的作用。方法 :以耐维A酸 (ATRA)早幼粒白血病细胞株MR2 为研究对象 ,以非耐药早幼粒白血病细胞株NB4为对照组 ,用免疫组化法观察P 糖蛋白 (Pgp)、多药耐药相关蛋白 (MRP)的表达。结果 :MR2 细胞Pgp表达 (30 %～ 4 0 % )较NB4细胞 (10 %～ 2 0 % )明显增强 (P <0 .0 0 1) ,MR2 细胞MRP表达 (6 0 .4± 4 .0～ 6 6 .5± 4 .4 )较NB4细胞 (2 8.3± 5 .6～ 31.2± 5 .1)明显增强 (P <0 .0 0 1)。 0 .5～ 2 .0μmol/L氧化砷能显著降低MR2 细胞Pgp、MRP表达。MR2 细胞Pgp、MRP表达的降低与氧化砷作用浓度和作用时间成负相关。结论 :MR2 细胞耐药蛋白Pgp、MRP表达的下调 ,可能是氧化砷克服耐药的敏感性指标。维A酸 (ATRA)可能是Pgp、MRP的转运底物。
Purpose:To detect the action of arsenic trioxide(As 2O 3) on the expression of tumor drug-resistant protein. Methods:APL cell line MR 2 resistant to all-trans retinoic acid(ATRA) was used for in vitro studies. APL cell line NB 4 was used for control. The expressions of P-glycoprotein(Pgp), multidrug resistance protein(MRP)were determined by immunocytochemical assays. Results:The expression of Pgp was significantly higher in MR 2 cell line(30%-40%) than in NB 4 cell line(10%-20%)(P<0.001),while the expression of MRP was obviously higher in MR 2 cell line(60.4±4.0-66.5±4.4) than in NB 4 cell line(28.3±5.6-31.2±5.1) (P<0.001). 0.5-2.0 μmol/l arsenic trioxide(As 2O 3) could significantly decrease the expressions of Pgp and MRP. The decreased Pgp and MRP expressions in MR 2 cell line was adversely dose-dependent and time dependent. Conclusions:The down-regulation of Pgp and MRP might be the sensitive target of arsenic trioxide(As 2O 3) to overcome drug-resistance in MR 2 cell line. ATRA might be the base substances of Pgp and MRP transmition action.
出处
《中国癌症杂志》
CAS
CSCD
2004年第4期357-359,362,共4页
China Oncology
