Effect of arsenic trioxide on drug transporting molecules in acute promyelocytic leukemia cell line.
- Author:
Xiao-ping QIAN
1
;
Bao-rui LIU
;
Hai-tao YIN
;
Li-feng WANG
;
Zheng-yun ZOU
;
Juan DU
Author Information
- Publication Type:Journal Article
- MeSH: ATP-Binding Cassette, Sub-Family B, Member 1; metabolism; Antineoplastic Agents; pharmacology; Arsenicals; pharmacology; Cell Line, Tumor; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Leukemia, Promyelocytic, Acute; metabolism; pathology; Multidrug Resistance-Associated Proteins; metabolism; Neoplasm Proteins; metabolism; Oxides; pharmacology; Tretinoin; pharmacology; Vault Ribonucleoprotein Particles; metabolism
- From: Chinese Journal of Oncology 2004;26(10):601-605
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo study the effect of arsenic trioxide (As2O3) on expression of drug transporting molecules in APL MR2 cell line.
METHODSMR2 resistant to all-trans retinoic acid (ATRA) and non-ATRA resistant APL cell line NB4 was used in this in vitro study. Expression of P-glycoprotein (Pgp), multidrug resistance protein (MRP) and lung resistance-related protein (LRP) was detected by immunocytochemical assay.
RESULTSThe expression of Pgp was significantly higher in MR2 (30%-40%) than in NB4 (10%-20%) (P < 0.001), and that of MRP was also higher in MR2 (56.9 +/- 3.4-21.2 +/- 1.1) than in NB4 (20.6 +/- 5.3-16.7 +/- 1.2) (P < 0.001). As2O3 at concentrations ranging from 0.5 approximately 2.0 micromol/L could significantly decrease the expression of Pgp and MRP, but not that of LRP. The decrease in the expression of Pgp and MRP in MR2 cell line was negatively correlated with the dose and duration of action of As2O3.
CONCLUSIONPgp and MRP, but not LRP, may be the sensitive targets of As2O3 to overcome drug-resistance. ATRA might be the substrates of Pgp and MRP.
