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The ability of synthetic interferon inducer, neovir (sodium 10-methylencarboxylate-9-acridone), was studied dealing with modulation of the sensitivity of HT-29 and K-562 cells, intact and transfected with mdr1 gene, in relation to the cytototoxic action of antitumor drugs. Neovir exerted the direct cytotoxic action on cells of all studied lines. Preliminary incubation of cells with neovir for 24 h efficiently increased the cytotoxic effect of doxorubicin and vincristine. The degree of toxicity enhancement was depended on the drug concentrations, as well as on cell lines. Neovir at the concentration 10 mg/ml had the most pronounced effect. The enhancement of toxic action of doxorubin for HT-29 cells had, as a rule, additive character, while for HT-29 MDR1 cells the interaction was synergistic (CD(50) was decreased by 2.85- and 8.67-fold respectively). The effect of vincristine toxicity enhancement didn't depend on mdr1 gene expression and had synergistic character. Neovir enhanced the cytotoxic effect of neovir in relation to K-562 and K-562 MDR1 cells by 3.18-fold and more than by 100-fold respectively. Also neovir increased the cytotoxic effect of 5-fluorouracil whose accumulation in cell doesn't depend on Pgp expression. Preliminary incubation of HT-29 cells with neovir has resulted in 2000-fold decrease of 5-fluorouracil CD(50) and in 36.6-fold for HT-29 MDR1 cells. Thus, the effect of neovir seems to have no relation to the action on the mechanisms of multiple drug resistance and may be mediated through some other pathways. |
