[Orphanin FQ combined with adriamycin reverses multi-drug resistance of K562/ADM and its molecular mechanism].
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.
The First Hospital of Lanzhou University, Lanzhou, Gansu Province, China.
Xiao-Xia
XX
Wang
Xiao-Qin
XQ
Liu
Wei
W
Zhang
Xuan
X
Chen
Li
L
Zhao
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D020014:K562 Cells; D018847:Opioid Peptides / Q000494:pharmacology*; D000097629:Nociceptin
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004317:Doxorubicin; D018847:Opioid Peptides; D000097629:Nociceptin; C513055:ABCB1 protein, human