Reversal of multidrug resistance in human liver cancer cells BEL-7402 by erythromycin / 中国药理学通报

ABSTRACT

AIM To study the reversal effect of erythromycin on multidrug resistance of human liver cancer cells BEL 7402. METHODS Cultivated the parental cells BEL 7402 in the presence of doxorubicin to obtain a multidrug resistant subline designated BEL 7402/ADM. The expression of P glycopro tein in BEL 7402 and BEL 7402/ADM cells was determined by using cell ELASA method. The cytotoxicity of drugs was determined by using MTT assay, and the intracellular concentration of doxorubicin in BEL 7402/ADM was determined using a spectrofluorometer. RESULTS After growing BEL 7402 cells in the presence of ADM for some time, the resulting cells (BEL 7402/ADM) became not only resistant to ADM but cross resistant to VCR and MMC, the P gp on the subline cells' surface was highly expresssed. Erythromycin, which is a lipophilic antibiotic, enhanced the anti tumor functions of ADM, VCR and MMC to BEL 7402/ADM cells and increased the intracellular concentration of ADM with no effect on the expression of the P gp in BEL 7402/ADM cells. CONCLUSUON Erythromycin can significantly reverse the multidrug resistance in BEL 7402/ADM cells, it may do so by saturating the P gp pathway to reduce the efflux of intracellular concentration of the drugs.