Growth inhibitory effects of pegylated IFN-α2b and 5-fluorouracil in combination on renal cell carcinoma cell lines in vitro and in vivo

Abstract

We investigated the effects of pegylated IFN-α2b (PEG-IFN-α2b) alone and PEG-IFN-α2b plus 5-fluorouracil (5-FU) in vitro on the proliferation of renal cell carcinoma (RCC) cell lines. After the transplantation of RCC cells into nude mice, we administered IFN (PEG-IFN-α2b or IFN-α2b) alone, 5-FU alone, or IFN (PEG-IFN-α2b or IFN-α2b) plus 5-FU; and investigated tumor volume, tumor weight, the numbers of apoptotic cells and artery-like blood vessels, relative mRNA expression levels of enzymes which relate to 5-FU metabolism, angiogenesis factor, and type I interferon receptor. RCC cells in vitro were generally and relatively resistant to the anti-proliferative effects of PEG-IFN-α2b, but the addition of 5-FU augmented IFN-induced anti-proliferative effects with the induction of apoptosis. PEG-IFN-α2b in vivo presented stronger anti-tumor effects than IFN-α2b, and its combination with 5-FU augmented the effects. The significant anti-tumor effect of the combination treatment was the increase in apoptotic cell number, but there were no significant differences in the suppression of angiogenesis, expression of IFN receptor, and the actions of metabolic enzymes of 5-FU. In conclusion, PEG-IFN-α2b presents stronger anti-tumor effects than non-pegylated IFN, and the effects are augmented in the combination with 5-FU. Our findings suggest the clinical usefulness of PEG-IFN-α2b in the treatment of RCC.