Reversal of adriamycin resistance by recombinant alpha-interferon in multidrug-resistant human colon carcinoma LoVo-doxorubicin cells.

Reversal of the drug resistance phenotype by the use of agents which induce cell differentiation offers an experimental approach to the study of chemoresistance. In numerous in vitro models, alpha-interferon (alpha-IFN) has been shown to induce phenotypical changes and to modulate the growth of cancer cells. The aim of the present study was to define the effect of alpha-IFN on the Adriamycin sensitivity of the human colon adenocarcinoma cell line, LoVo, and its Adriamycin-resistant variant, LoVo/DX. Pretreatment of LoVo/DX cells with 500 units/ml of alpha-IFN increased sensitivity to low doses of Adriamycin. Similar treatment conditions did not change the sensitivity of the parental cell line. Following treatment of the LoVo/DX cells with alpha-IFN plus 100 ng/ml Adriamycin for 1 h, 30% of the cells survived compared to 100% of untreated cells. This effect was not related to changes in cell cycle kinetics induced by alpha-IFN treatment and did not result from variations in the expression of P-glycoprotein at the cell surface, as assessed by flow cytometric analysis using monoclonal antibody MRK16. Adriamycin accumulation was increased by alpha-IFN as assessed by spectrofluorometric analysis. Thus, the data suggest that in LoVo/DX cells, alpha-IFN increased Adriamycin cytotoxicity through modulation of the multidrug resistance phenotype.