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

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Abstract

Interferon (IFN) is known as a multifunctional cytokine. The aim of this study was to examine the different effects of IFN subclass; namely, IFN-α and IFN-β, 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-α, IFN-β 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-β significantly inhibited HCC growth whereas the same dose of IFN-α did not. IFN-β also significantly suppressed the tumor growth both in the p53-wild and p53-mutant HCC cells. Our in vitro study revealed that IFN-β showed a more potent inhibitory effect on the endothelial cell proliferation than IFN-α 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-α and IFN-β exert tumoricidal effects of different magnitudes on HCC.

identifier:International Journal of Oncology Vol.32 No.1 pp.193-199

identifier:10196439

identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/2321

identifier:International Journal of Oncology, 32(1): 193-199

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