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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。
Objective: To investigate the effect of arsenic trioxide (As_2O_3) on tumor drug resistance. Methods: The ATRA-resistant promyelocytic leukemia cell line MR_2 was used as the research object. The non-drug resistant acute promyelocytic leukemia cell line NB_4 was used as the control group. The expression of P-glycoprotein Pgp), glutathione S transferase (GST). Results: Compared with NB4 cells (10% -20%), the expression of Pgp in MR2 cells was significantly increased (P <0.001), and the expression of GSTπ in MR2 cells (60.4 ± 4.0) ~ (66.5 ± 4.4) 28.3 ± 5.6) ~ (31.2 ± 5.1) (P <0.05). 0.5 ~ 2.0μmol / L As_2O_3 could significantly reduce the expression of Pgp and GSTπ in MR_2 cells, but had no effect on GSTα and GSTμ. Conclusion: The down-regulation of Pgp and GSTπ expression may be the sensitive index to overcome the resistance of As_2O_3, while GSTα and GSTμ are not. All-trans retinoic acid (ATRA) may be Pgp transport substrate and GSTπ catalytic substrate.