Cytotoxicity of Combinations of IFN- β and Chemotherapeutic Drugs

Abstract

Interferon-β (IFN-β) induces various antiproliferative activities. In solid tumor cells, IFN-β inhibits cell cycle progression, which mainly occurs as S phase accumulation. The IFN-β-induced cell cycle effect has been implicated in the antitumor effect of combinations of IFN-β and chemotherapeutic drugs. In this report, we characterized the viability of various human tumor cells in vitro after combination treatment with IFN-β protein and the chemotherapeutic drugs, cis-platinum (II) diamine dichloride (cisplatin), 5-fluorouracil (5-FU), paclitaxel (Taxol) and gemcitabine. IFN-β could significantly potentiate the cytotoxicity of these chemotherapeutic drugs. The potentiating effect was observed after pretreatment of tumor cells with IFN-β but did not require the constant presence of IFN-β. The potentiating effect correlated with the sensitivity of the tumor cells to the IFN-β-induced cytotoxicity. Furthermore, chemotherapeutic drugs also potentiated the cytotoxicity of IFN-β. We conclude that the cell cycle effect per se did not determine the ability of IFN-β to potentiate the cytotoxicity of chemotherapeutic drugs. We suggest that the combination of local IFN-β gene therapy with chemotherapy could be an effective cancer treatment.