氧化砷对MR2细胞耐药分子表达的影响

目的:探讨三氧化二砷(As_2O_3)对肿瘤耐药分子的作用。方法:以耐全反式维甲酸(ATRA)早幼粒白血病细胞株MR_2为研究对象,以非耐药急性早幼粒白血病细胞株NB_4为对照组,用免疫组化法观察P-糖蛋白(Pgp)、谷胱甘肽S转移酶(GST)的表达。结果:MR_2细胞Pgp表达(30％～40％)较NB_4细胞(10％～20％)明显增强(P<0.001),MR_2细胞GSTπ表达(60.4±4.0)～(66.5±4.4)较NB_4细胞(28.3±5.6)～(31.2±5.1)明显增强(P<0.05)。0.5～2.0μmol/L As_2O_3能显著降低MR_2细胞Pgp、GSTπ表达,而对GSTα、GSTμ无影响。结论:Pgp、GSTπ表达的下调,可能是As_2O_3克服耐药的敏感性指标,而GSTα、GSTμ则否。全反式维甲酸(ATRA)可能是Pgp转运底物和GSTπ催化作用底物。

The Effect of As2O3 on the Epression of Drug-resistance Molecule in Malignant Neoplasmas

Objective: To detect the action of arsenic trioxide (As2 O3 ) on the expressionof Tumor drug-resistant molecule. Methods: APL cell line MR2 resistant to all-trans retinoic acid (ATRA) was put into research, while APL cell line NB4 was used for control. The immunocytochemical assays were used to detect the expressions of P-glycoprotein ( Pgp ) and Glutathione S-transferase (GST). Results: Not only the expression of Pgp in MR2 cell linw (30%-40%) was significantly higher than that in NB4 cell linc (10%-20%) (p ＜ 0.001), but also the expression of GST in MR2 cell linc (60.4 ± 4.0)- (66.5 ± 4.4) was significantly higher than that in NB4 cell linc (28.3 ± 5.6)- (31.2 ± 5.1) ( P ＜ 0.05). As2 O3 at the concentration of 0.5-2.0μmol/l could significantly aecrease the expression of Pgp and GSTπ, but could do nothing about the expression of GSTα and GSTμ . Conclusion: The lower expression of Pgp and GSTπ might be the sensitive indications of frustrating drug-resistance, while GSTα and GSTμ might not be the case. ATRA might be the substrates of Pgp transmission and GSTπ catalysis.