[Effect of arsenic trioxide on drug transporting molecules in acute promyelocytic leukemia cell line].
OBJECTIVE
To study the effect of arsenic trioxide (As2O3) on expression of drug transporting molecules in APL MR2 cell line.


METHODS
MR2 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.


RESULTS
The 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.


CONCLUSIONS
Pgp 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.
Qian
Xiao-ping
XP
Department of Oncology, Nanjing Drum Tower Hospital, Nanjing University of Chinese Medicine, Nanjing 210008, China. Qianxiaoping211@hotmail.com
Liu
Bao-rui
BR
Yin
Hai-tao
HT
Wang
Li-feng
LF
Zou
Zheng-yun
ZY
Du
Juan
J
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006801:Humans; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism* / Q000473:pathology; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D010087:Oxides / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology; D020394:Vault Ribonucleoprotein Particles / Q000378:metabolism*; D000099187:Major Vault Protein
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D000077237:Arsenic Trioxide; D001152:Arsenicals; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D010087:Oxides; D014212:Tretinoin; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein