Interferon-alpha 2b modulation of doxorubicin sensitivity in a multidrug resistant cell line.
We evaluated the effect of interferon-alpha2b as a chemosensitiser on HCT-15 cell line in treatment with doxorubicin. Chemosensitivity was determined by [3H]-thymidine incorporation and tetrazolium assays. The levels of expression of P-glycoprotein, Bcl-2 oncoprotein and HLA-ABC complex, and cell cycle/apoptosis analysis were determined by flow cytometry. Dox 50 ng/ml - IFN alpha 2b 500 IU/ml treatment inhibited cell proliferation (47.2 +/- 1.4%, p < 0.0001; MTT assay: 40.6 +/- 1.2%, p < 0.0001) and augmented the expression of P-170, Bcl-2 and HLA-ABC, while it didn't exert apoptosis, producing a slight G2/M arrest. A concentration of IFN-alpha2b, that by itself is not cytotoxic, can potentiate the efficacy of the anticancer drug. This effect is not due to a down-modulation of P-170. The absence of apoptosis and augmented levels of Bcl-2 expression suggests that this could be one of the mechanisms of drug resistance exerted by these cells.
Lucero Gritti
M F
MF
Laboratorio de Inmunología', Instituto de Biologia y Medicina Experimental (CONICET), Buenos Aires, Argentina.
Beviacqua
M
M
Bordenave
R H
RH
Rumi
L S
LS
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000230:Adenocarcinoma; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms; D004317:Doxorubicin / Q000633:toxicity*; D018432:Drug Resistance, Multiple / Q000502:physiology; D004357:Drug Synergism; D016195:G2 Phase; D006680:HLA Antigens / Q000032:analysis; D015234:HLA-A Antigens / Q000032:analysis; D015236:HLA-C Antigens / Q000032:analysis; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000032:analysis; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D008565:Membrane Proteins; D008938:Mitosis; D050722:Oncogene Protein v-cbl; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; C103673:HFE protein, human; D006680:HLA Antigens; D015234:HLA-A Antigens; D015236:HLA-C Antigens; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008565:Membrane Proteins; D050722:Oncogene Protein v-cbl; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; D004317:Doxorubicin