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, α-interferon (α-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 α-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 α-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 α-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 α-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 α-IFN as assessed by spectrofluorometric analysis. Thus, the data suggest that in LoVo/DX cells, α-IFN increased Adriamycin cytotoxicity through modulation of the multidrug resistance phenotype.
|Number of pages||5|
|Publication status||Published - Sep 15 1991|
ASJC Scopus subject areas
- Cancer Research