Noguchi Ryuichi, Yoshiji Hitoshi, Ikenaka Yasuhide, Kitade Mitsuteru, Kaji Kosuke, Yoshi Junichi, Yanase Koji, Namisaki Tadashi, Yamazaki Masaharu, Tsujimoto Tatsuhiro, Akahane Takemi, Uemura Masahito, Fukui Hiroshi
Third Department of Internal Medicine, Nara Medical University, Nara, Japan.
Int J Oncol. 2008 Jan;32(1):193-9.
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-alpha, 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-alpha 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-alpha and IFN-beta exert tumoricidal effects of different magnitudes on HCC.
干扰素（IFN）是一种多功能细胞因子。本研究的目的是检测IFN亚类，即IFN-α和IFN-β，对肝细胞癌（HCC）生长的不同影响，特别是与在肿瘤生长中起关键作用的血管生成相关的影响。此外，我们还研究了肿瘤中的p53状态是否会改变IFN对HCC生长的抗肿瘤作用，因为据报道p53状态会影响抗血管生成药物对癌症的治疗效果。与IFN-α相比，IFN-β对HCC生长具有更强的抑制作用，即使在肿瘤形成后也是如此，同时还能抑制肿瘤中的新血管形成。临床可比低剂量的IFN-β单次治疗可显著抑制HCC生长，而相同剂量的IFN-α则无此作用。IFN-β在p53野生型和p53突变型HCC细胞中均能显著抑制肿瘤生长。我们的体外研究表明，与体内研究一样，IFN-β对内皮细胞增殖的抑制作用比IFN-α更强。总体而言，IFN可能是一种针对HCC的替代抗血管生成药物，因为即使在低剂量下，它也能发挥显著的杀肿瘤作用，且与宿主p53状态无关。在临床实践中也可能需要谨慎对待，因为即使在同一IFN亚类（I类）中，IFN-α和IFN-β对HCC的杀肿瘤作用程度也不同。
