Different tumoricidal effects of interferon subclasses and p53 status on hepatocellular carcinoma development and neovascularization

作者：Noguchi Ryuichi; Yoshiji Hitoshi^*; Ikenaka Yasuhide; Kitade Mitsuteru; Kaji Kosuke; Yoshii Junichi; Yanase Koji; Namisaki Tadashi; Yamazaki Masaharu; Tsujimoto Tatsuhiro; Akahane Takemi; Uemura Masahito; Fukui Hiroshi

来源：International Journal of Oncology, 2008, 32(1): 193-199.

• angiogenesis
• interferon
• hepatocellular carcinoma
• p53
• vascular endothelial cell growth factor

Interferon (IFN) is known as a multifunctional cytokine. The aim of this study was to examine the different effects of IFN subclass; namely, IFN-alpha and IFN-beta, on hepatocellular carcinoma (HCC) growth especially in conjunction with angiogenesis that is known to play a pivotal role in the tumor growth. Furthermore, we also examined whether the p53 status in the tumor would alter the anti-tumoral effect of IFN against HCC growth since the p53 status reportedly affected the therapeutic effect of anti-angiogenic agents against cancer. When compared with IFN-a, IFN-beta exerted a more potent inhibitory effect on HCC growth, even after the tumor was established, along with suppression of neovascularization in the tumor. A single treatment with clinically comparable low doses of IFN-beta significantly inhibited HCC growth whereas the same dose of IFN-alpha did not. IFN-beta also significantly suppressed the tumor growth both in the p53-wild and p53-mutant HCC cells. Our in vitro study revealed that IFN-beta showed a more potent inhibitory effect on the endothelial cell proliferation than IFN-a as in the in vivo study. Collectively, IFN may be an alternative anti-angiogenic agent against HCC since it exerted a significant tumoricidal effect regardless of the host p53 status even at a low dose. A cautious approach may be also required in the clinical practice since even in a same IFN subclass (class-I), IFN-a and IFN-beta exert tumoricidal effects of different magnitudes on HCC.

• 出版日期2008-1