Recombinant human interleukin 24 reverses Adriamycin resistance in a human breast cancer cell line

Abstract

BackgroundThe major cause of multidrug resistance is over-expression of membrane P-glycoprotein (P-gp). We investigated the effect of recombinant human interleukin 24 (rhIL-24) on the Adriamycin (ADM)-resistant human breast cancer cell line MCF-7/ADM. MethodsThe cytotoxicity of rhIL-24 and ADM was determined by 3-[4,5-dimethylthiazol-2-yl], 5-diphenyl tetrazolium bromide (MTT) assays. The expression of P-gp was assessed by confocal microscopy and Western blot analysis. ResultsThe IC50 values for rhIL-24 in MCF-7/wild-type and MCF-7/ADM cells were 0.17 and 14.6μM, respectively. The IC50 value of Adriamycin in MCF-7/ADM cells decreased in a dose-dependent manner when rhIL-24 was used. The resistance modulating factor (RMF) was directly proportional to the dose of rhIL24. ADM accumulation increased while P-gp expression decreased at a low dose (4μM) of rhIL24 in MCF-7/ADM cells. The expression of P-gp was decreased at 4μM in confocal microscopy and western blot analysis. ConclusionsrhIL-24 circumvented the drug-resistance of MCF-7/ADM cells via activation of the transcription factor Stat 3. rhIl24 has potential to act as a P-gp inhibitor to reverse Adriamycin resistance in breast cancer.