[Mechanism reversing MDR of K562/A02 by garlicin combined with erythromycin]

Abstract

This study was purposed to investigate the reversal effect of garlicin, erythromycin alone or combination of garlicin with erythromycin on K562/A02 and its possible mechanisms, so as to provide experimental evidence for combination reversal strategies. Cytotoxicity and the reversal effect of garlicin and erythromycin alone and combination of this two drugs were detected by MTT assay. The expression of mdr1 gene of K562/A02 was detected by RT-PCR. The P-gp expression was observed by immunohistochemical technique. Flow cytometry was used to detect intracellular drug concentration. The results showed that the sensitivity of K562/A02 to ADM increased somewhat in the presence of 1, 4, 8 mg/L garlicin, the reversal multiples at 1, 4, 8 mg/L garlicin were 1.80, 2.26 and 2.82 respectively in dose-dependent manner. The reversal multiple of erythromycin 60 mg/L was 2.20. The combination of two drugs could increase the reversal multiple to 4.94, and had no more cytotoxin. Both of garlicin and erythromycin alone could down-regulate the expression of mdr1 and P-gp of K562/A02 and elevate the intracellular concentrations of ADM in K562/A02 cells. Meanwhile, the effects described above were enhanced when garlicin was combined with erythromycin. It is concluded that the garlicin and erythromycin alone under cytotoxic dose both can reverse the MDR of K562/A02 cells effectively. Moreover, the combination of two drugs is more effective than that in use alone. Combination of these two drugs shows synergistic actions in regulating the expression of mdr1/P-gp and increasing the intracellular concentrations of ADM in K562/A02 cell.