Polyoxyethylene 40 stearate modulates multidrug resistance and enhances antitumor activity of vinblastine sulfate

Abstract

Multidrug resistance (MDR) is one of the major obstacles limiting the efficacy of cancer chemotherapy. Identification of new and effective MDR reversal agents is needed. In this study, the effects of polyoxyethylene 40 stearate (PS40) on MDR were evaluated via the transport of the P-glycoprotein (P-gp) substrate vinblastine sulfate (VBL) through Caco-2 cell monolayers and rat intestine tissue. The effects of PS40 on the antitumor activity of VBL were examined through 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay and multidrug-resistant tumor-bearing mice. Results of the transport experiments showed that PS40 reduced VBL efflux. The cytotoxicity of vinblastine to K562/ADR cells was significantly enhanced when the cells were cotreated with 100 or 150 microg/mL PS40. In vivo data revealed that average tumor volume and average tumor weight were significantly less in the VBL+PS40 group than in the VBL group. The inhibition rate for tumor growth was increased from 0.06 (VBL group) to 0.84 (VBL+PS40 group). These results suggest that PS40 may be a potentially useful adjuvant to enhance the therapeutic effects of P-gp substrates.