Interferon- β Augments the Effects of Cisplatin on Hcc Cell Lines by Regulating Sub Cellular Localization of P21
- Gastroenterology & Hepatology: Open Access
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Masahiko Yano1, Shogo Ohkoshi2*, Hajime Hara2, Haruka Hirono2, Kazuhiko Watanabe2, Katsuhiko Hasegawa2, Yasunobu Matsuda1 and Yutaka Aoyagi1
Department of Internal Medicine, The Nippon Dental University, Japan - Masahiko Yano, Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences of Niigata University, Japan
- Hajime Hara, Department of Internal Medicine, The Nippon Dental University, Japan
- Haruka Hirono, Department of Internal Medicine, The Nippon Dental University, Japan
- Kazuhiko Watanabe, Department of Internal Medicine, The Nippon Dental University, Japan
- Katsuhiko Hasegawa, Department of Internal Medicine, The Nippon Dental University, Japan
- Yasunobu Matsuda, Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences of Niigata University, Japan
- Yutaka Aoyagi, Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences of Niigata University, Japan
Abstract
Introduction: Interferon (IFN) has been used for patients with advanced hepatocellular carcinoma (HCC) in combination with chemotherapeutic agents. We previously reported that IFN-? induced a shift into the nucleus of Cytoplasmic p21 (Cip1/WAF1), known as a tumor-suppressor gene, and contributed to the prevention of HCC.
Aims: To use hepatoma cell lines to compare the growth-suppression activity of IFN-? and ?, in the context of enhancing cisplatin’s effects.
Results: IFN-? caused a significant nuclear localization of p21 when compared to IFN-? IFN-? augmented the cytotoxic effects of cisplatin more than IFN- ?. Notably, when IFN-? was used only for pre-treatment, significant apoptosis with subsequent cisplatin treatment was observed.
Conclusion: Results suggest that IFN- ? enhances the cytotoxic effects of cisplatin more than IFN-?, partly because of its effect of keeping p21 in the nucleus. Thus, IFN-?-based chemo-therapeutic regimen might provide more effective outcomes of HCC treatment.
Keywords
Hepatocellular carcinoma, p21 (Cip1/WAF1), IFN- ? , Cisplatin, Subcellular localization, Apoptosis, 5-fluolouracil, Cell-viability tests, Cytoplasm, Hepatitis B virus
