Valproic Acid Enhances the Anti-tumor Effect of Pegylated Interferon-α Towards Pancreatic Cancer Cell Lines

Background: Valproic acid (VPA) acts as a specific inhibitor of class I HDACs and it use has been proven to be safe since a long time. Materials and Methods: In the present study, we investigated the effect of VPA in the combination with pegylated interferon-α (PEG-IFNα) in inhibition of cell proliferation of human pancreatic cancer cell lines. Results: VPA enhanced the effect of PEG-IFNα, and the effect was decreased by the caspase inhibitor. VPA alone and VPA in combination with PEG-IFNα increased the expression of interferon-α receptor and interferon regulatory factor 8. Conclusion: The combination of VPA and PEG- IFNα can be useful for the treatment of pancreatic cancer. Pancreatic cancer is the fifth leading cause of death related to cancer in Japan. Surgery is the sole curative therapy, and for advanced pancreatic cancer, surgical resection is followed by adjuvant chemotherapy. However, the response rates to chemotherapy are below 20%, with a median life expectancy of 19 months (1, 2). The statistics for second-line therapy are even more dismal, with response rates <10% and median survival of 4 months (3). So, it is imperative to improve the chemotherapy in the management of pancreatic cancer. Recently, it has been reported (4) that interferon-α (IFNα) in combination with adjuvant chemoradiotherapy improved 5-year survival to 55%, and IFNα seems to play a crucial role in these treatment regimens (5).