Using protein chips to study mechanism underlying reversion of drug resistance in leukemia cells in tetrandrine alone or in combination with droloxifene.
- Author:
Bao-An CHEN
1
;
Juan DU
;
Chun-Xiu ZHANG
;
Jian CHENG
;
Feng GAO
;
Zu-Hong LU
Author Information
1. Department of Hematology, Zhongda Hospital, Southeast University Medical College, Nanjing 210009, China. cba8888@hotmail.com
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter, Sub-Family G, Member 2;
ATP-Binding Cassette Transporters;
biosynthesis;
ATP-Binding Cassette, Sub-Family B, Member 1;
biosynthesis;
Antineoplastic Agents;
pharmacology;
Benzylisoquinolines;
pharmacology;
Drug Resistance, Multiple;
Drug Resistance, Neoplasm;
drug effects;
Drug Synergism;
Humans;
K562 Cells;
Leukemia;
metabolism;
pathology;
Multidrug Resistance-Associated Proteins;
biosynthesis;
Neoplasm Proteins;
biosynthesis;
Protein Array Analysis;
Tamoxifen;
analogs & derivatives;
pharmacology
- From:
Journal of Experimental Hematology
2005;13(6):999-1003
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study was to investigate the mechanism to reverse the drug resistance of leukemia cells in tetrandrine (Tet) alone or in combination with droloxifen (Drol) by using protein chips and to lay the theoretical basis for the clinical applications. Three monoclonal antibodies against P-glycoprotein (P-gp), the multidrug resistance-associated protein (MRP1) and the breast cancer resistance protein (BCRP) were immobilized onto the agarose gel film-coated glass slides. Protein chips were prepared respectively from K562/A02 cells cultured for 12, 24 and 48 hours with Tet alone or in combination with Drol. The results showed that Tet alone or in combination with Drol could decrease only the expression of P-gp in a time-dependent manner, the effect for 48 hours as follows: Tet + Drol 82.620 +/- 3.227; Tet alone 86.440 +/- 2.906; Drol alone 87.230 +/- 2.049; control 93.670 +/- 2.748 (P < 0.05). However, down-regulation of P-gp by K562/A02 cells cultured with Tet alone or in combination with Drol began at 24 hours (Tet + Drol 85.270 +/- 3.095; control 93.670 +/- 2.748, P < 0.05). The results were coincident with that of FCM. It is concluded that Tet and Drol can downregulate the expression of P-gp in the time-dependent way. There is a significant difference between Tet alone and Tet combined with Drol at 24 hours (P < 0.05). The expression of MRP1 and BCRP are not closely correlated with the reversal mechanism of Tet and Drol, and which may be involved in the mechanism of this combination to reverse multidrug resistance in leukemia.
