SYNERGISM BETWEEN GAMMA INTEFERON AND DOXORUBICIN IN A HUMAN MDR COLON ADENOCARCINOMA CELL-LINE

Recent interest in cancer therapy derives from the ability of interfer ons to synergistically increase the activity of chemotherapeutic agent s. To understand the biological basis of this synergism we evaluated t he effects of human recombinant IFN-gamma on the expression of the mdr l gene and on the cellular growth of a human colon adenocarcinoma cell line (Lo Vo) and its MDR subline (Lo Vo/Dx) after coincubation with d oxorubicin. Treatment with IFN-gamma showed unchanged levels of MDR1-g lycoprotein, no perturbation on cell cycle distribution and a signific ant reduction of colony formation in both lines (P<0.05) starting from 100 U/ml. A synergistic effect was observed in the LoVo/Dx cell line when doxorubicin was added after exposure to 0.1-10 U/ml of IFN-gamma. Our data indicate that the effects of IFN-gamma, independent from act ion on cell proliferation and from modulation of p-glycoprotein expres sion, are a cause of the synergistic activity between this lymphokine and conventional chemotherapeutic agents such as doxorubicin.