Effect and mechanism of nociceptin/orphanin FQ reversing multi-drug resistance in K562/ADM cell
Li, Z.; Zhou, L.-X.; Zhang, B.-H.; Yan, X.; Li, J.; Peng, Y.-L.; Chang, M.; Dong, S.-L.; Wang, R.
Die Pharmazie 63(9): 676-685
2008
ISSN/ISBN: 0031-7144 PMID: 18819522 Document Number: 616897
To investigate the effect and mechanism of nociceptin/orphanin FQ (OFQ) reversing multi-drug resistance of K562/ADM cells in vitro. MTT assay, Wright staining, flow cytometry, transmission electron microscope and gel electrophoresis were used to evaluate the effect and mechanism of OFQ in reversing multi-drug resistance of K562/ADM cells. OFQ could time-dependently reverse the ADM resistance of K562/ADM cell. After treatment with OFQ (1 x 10(-7) mol x L(-1)), K562/ADM cells were cultured for 24, 48 and 72 h. The reversal index (RI) was 1.33, 1.42 and 1.53, respectively. Furthermore, OFQ significantly increased the intracellular accumulation of ADM in K562/ADM cells and percentage apoptosis in K562/ADM cells. OFQ down-regulated the level of P-gp time-dependently, while the level of Fas and FasL were up-regulated. There were evidently significant differences compared with the control (P < 0.01). After treating K562/ADM cells with OFQ (1 x 10(-7) mol x L(-1)) and ADM (20 microg x ml(-1)) for 48 hours, the cells showed apoptotic nuclear fragmentation, which was characterized by the appearance of a DNA ladder pattern in genomic DNA gel electrophoresis. OFQ can reverse the ADM resistance of K562/ADM cells. The mechanism involves OFQ up-regulating the expression of Fas/FasL, down-regulating the level of P-gp, and decreasing the intracellular level of calcium in K562/ADM cells.