title: Reversal of adriamycin resistance by recombinant alpha-interferon in multidrug-resistant human colon carcinoma LoVo-doxorubicin cells.
abstract: 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.
authors.affiliation: Cattedra di Oncologia Medica, II Facoltà di Medicina, Università di Napoli, Naples, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Scala
authors.forename: R
authors.initials: R
authors.lastname: Pacelli
authors.forename: R V
authors.initials: RV
authors.lastname: Iaffaioli
authors.forename: N
authors.initials: N
authors.lastname: Normanno
authors.forename: S
authors.initials: S
authors.lastname: Pepe
authors.forename: G
authors.initials: G
authors.lastname: Frasci
authors.forename: G
authors.initials: G
authors.lastname: Genua
authors.forename: T
authors.initials: T
authors.lastname: Tsuruo
authors.forename: P
authors.initials: P
authors.lastname: Tagliaferri
authors.forename: A R
authors.initials: AR
authors.lastname: Bianco
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000494:pharmacology*; D004351:Drug Resistance / Q000235:genetics; D004354:Drug Screening Assays, Antitumor; D015870:Gene Expression; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
chemical_list: D007370:Interferon Type I; D008562:Membrane Glycoproteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D004317:Doxorubicin