Interferon-β is more potent than interferon-α in inhibition of human hepatocellular carcinoma cell growth when used alone and in combination with anticancer drugs

Background: The prognosis of advanced hepatocellular carcinoma (HCC) is extremely poor, but promising effects of chemotherapies combined with interferon (IFN) have been reported. Methods: To develop more effective combination therapies for HCC, we compared the antiproliferative effects of IFN-alpha and IFN-beta in combination with various cytotoxic drugs on hepatoma cell lines using MTT assay and isobologram analysis. Results: IFN-beta was more potent than IFN-alpha in inhibiting the cell growth of all cell lines (P <.05, two-way ANOVA). PLC/PRF/5 was more sensitive to either IFN, than HLE and HuH7. Cell growth of all cell lines was inhibited in a dose-dependent manner by 5-fluorouracil (5-FU), cisplatin (CDDP), and doxorubicin (DOX), but the sensitivities of these cells were considerably different. As for IFN-α, synergistic effects were observed when combined with 5-FU and DOX on PLC/PRF/5 cells only, whereas IFN-β showed synergistic effects with 5-FU and CDDP on HuH7 and PLC/ PRF/5 cell lines. Conclusion: The spectra of the antiproliferative activity and synergistic effect of IFN-β when combined with anticancer drugs are more potent than those of IFN-α. Combinations of IFN-β and anticancer drugs may provide a better treatment of HCC when combinations with IFN-α are ineffective.