Kohashi Shigechika, Sato Yuji, Fukushima Tsuyoshi, Shomura Hiroki, Oshima Takahiro, Bairun Sun, Kondo Masao, Une Yoshie, Nishihira Jun, Todo Satoru
Department of Gastroenterological and General Surgery, Hokkaido University School of Medicine, N15-W7 Kita-ku, Sapporo, 060-8638, Japan.
Surg Today. 2007;37(6):474-81. doi: 10.1007/s00595-006-3418-z. Epub 2007 May 28.
The antitumor effects of Interferon-beta (IFN-beta) are due to its direct inhibition of cell proliferation, immunostimulatory activity, and the inhibition of angiogenesis. We investigated the mechanism of the effects of IFN-beta on a murine colon 26 cell line (CT 26) and its highly metastatic variant (L5).
We examined its inhibitory effects on cell proliferation in vitro and the development of liver metastases in vivo.
The proliferation of CT 26 in vitro was inhibited by IFN-beta in a dose- and time-dependent manner. The number of metastases was reduced in mice inoculated with CT 26 (P<0.01) and L5 (P<0.01) on Day 14 after treatment with IFN-beta. The median survival rate of the mice inoculated with L5 administered IFN-beta every other day, or every day was higher than in the control group (P<0.05). A dorsal air sac assay demonstrated that IFN-beta inhibited angiogenesis in mice inoculated with CT 26, but the effects disappeared with aminoguanidine, an inducible nitric oxide synthase inhibitor.
These results showed that IFN-beta directly inhibits the proliferation of CT 26. In addition, the in vivo experiments suggested that IFN-beta might effectively inhibit liver metastases.
β-干扰素(IFN-β)的抗肿瘤作用归因于其对细胞增殖的直接抑制、免疫刺激活性以及对血管生成的抑制。我们研究了IFN-β对小鼠结肠26细胞系(CT 26)及其高转移性变体(L5)作用的机制。
我们检测了其对体外细胞增殖和体内肝转移发生的抑制作用。
IFN-β以剂量和时间依赖性方式抑制CT 26的体外增殖。在用IFN-β治疗后第14天,接种CT 26(P<0.01)和L5(P<0.01)的小鼠转移灶数量减少。每隔一天或每天给予IFN-β的接种L5小鼠的中位生存率高于对照组(P<0.05)。背囊试验表明,IFN-β抑制接种CT 26小鼠的血管生成,但用诱导型一氧化氮合酶抑制剂氨基胍处理后,该作用消失。
这些结果表明,IFN-β直接抑制CT 26的增殖。此外,体内实验提示,IFN-β可能有效抑制肝转移。