Orphanin FQ combined with adriamycin reverses multi-drug resistance of K562/ADM and its molecular mechanism.
- Author:
Xiao-Xia WANG
1
;
Xiao-Qin LIU
;
Wei ZHANG
;
Xuan CHEN
;
Li ZHAO
Author Information
1. The First Hospital of Lanzhou University, Lanzhou, Gansu Province, China.
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter, Sub-Family B;
ATP-Binding Cassette, Sub-Family B, Member 1;
metabolism;
Doxorubicin;
pharmacology;
Drug Resistance, Multiple;
drug effects;
Drug Resistance, Neoplasm;
drug effects;
Humans;
K562 Cells;
Opioid Peptides;
pharmacology
- From:
Journal of Experimental Hematology
2012;20(3):574-578
- CountryChina
- Language:Chinese
-
Abstract:
Our study have confirmed that orphanin FQ (OFQ) alone can reverse the multi-drug resistance of K562/ADM at the cellular level. Thus, this study was purposed to investigate the molecular mechanism of OFQ combined with ADM that reverses multi-drug resistance of K562/ADM, as well as its correlation with the expression of MDR1 mRNA and P-glycoprotein (P-gp). MTT method was used to detect the proliferation ability of K562/ADM treated with OFQ and ADM alone and their combination; flow cytometry was performed to measure the cell apoptosis rate; real time-PCR was applied to detect the MDR1 mRAN expression; Western blot was used to determine the P-gp expression. The results showed that OFQ (0.1 µmol/L) combined with ADM (15 mg/L) significantly inhibited the cell proliferation of K562/ADM, compared with ADM group; the date gained at 48 h was statistically significant (P < 0.05), and cell apoptosis rate was significantly raised (P < 0.01); MDR1 mRNA and P-gp expression levels of OFR combined with ADM were significantly lower than that of ADM alone, and were time-dependent within 48 h. It is concluded that OFQ combined with ADM can reverse the multi-drug resistance of K562/ADM in time-dependent manner, and the 48 h after treatment with these 2 drugs is the best reverse time, which may be related with down regulating the expression of MDR1 mRNA and P-gp.
