Establishment of therapeutic methods against oral cancer using interferon-gamma gene

干扰素-γ是一种多功能细胞因子，其主要作用包括抑制癌细胞的增殖和调节癌细胞表面某些细胞黏附分子的表达。虽然已知干扰素-γ的这些功能在宿主抗癌免疫功能中具有重要作用，但对干扰素-γ在癌细胞转移过程中的重要作用知之甚少。本研究的目的是利用干扰素-γ受体基因敲除小鼠(干扰素-γR0/0小鼠)，探讨干扰素-γ在肿瘤细胞转移特性中的重要作用。野生型(WT)和干扰素-γR0/0小鼠均尾静脉注射高转移性黑色素瘤B16细胞1×10_5。注射三周后，处死小鼠，取脾、肺和肝脏，在显微镜下比较转移的程度。结果表明，与静脉注射干扰素-γR0/0小鼠相比，WT小鼠器官中的B16细胞更为丰富。WT组小鼠腹膜腔内B16细胞的数量明显多于腹腔注射干扰素-γR0/0组。静脉注射B16细胞3周后，从外周血中分离血清，用ELISA法测定细胞因子水平。WT小鼠和干扰素-γR0/0小鼠血清IL-1α、IL-6和肿瘤坏死因子水平无统计学差异。小鼠血清IL-1α、IL-6、IL-12和肿瘤坏死因子水平在WT小鼠和干扰素-γR0/0小鼠之间差异无统计学意义。干扰素-γR0/0组小鼠脾组织中IL-12mRNA水平高于WT组小鼠。WT和干扰素-γR0/0小鼠的血清一氧化氮水平也没有明显差异，一氧化氮是激活的巨噬细胞的细胞毒效应分子。这些结果表明，小鼠在没有干扰素-γ的情况下可以抵抗肿瘤的转移。

Interferon-gamma (IFN-gamma) is an multifunctional cytokine whose major actions include inhibition of proliferation of cancer cells and regulation of the expression of some cell adhesion molecules on cancer cells. Although these functions of IFN-gamma are known to be important in host immune functions against cancer, little is known about the essential role of IFN-gamma in the course of metastasis of cancer cells. The purpose of this study is to investigate the essential role of IFN-gamma on the metastatic property of cancer cells, using IFN-gamma receptor gene knock-out mice (IFN-gamma R0/0 mice). Both wild-type (WT) and IFN-gamma R0/0 mice were injected in to the tail vein, or i.p.with 1*10_5 of B16 cells, highly metastatic melanoma cells. Three weeks after injection, mice were killed and spleens, lungs and livers were removed from both types of mice and the extent of metastasis was compared microscopically. As a results, B16 cells were more abundant in the organs removed from WT mice than there removed from IFN-gamma R0/0 mice which are injected intravenously. B16 cells were more abundant in the periotoneal cavity of WT mice than that of IFN-gamma R0/0 mice which are injected i.p. Three weeks after intravenous injection of B16 cells, serum was also separated from peripheral blood and cytokine levels were determined by ELISA.there were no statistical differences in serum levels of IL-1alpha, IL-6 and TNF between WT and IFN-gamma R0/0 mice. There were no statistical differences in serum levels of IL-1alpha, IL-6, IL-12 and TNF between WT and IFN-gamma R0/0 mice. IL-12 mRNA levels in spleen from IFN-gamma R0/0 were hihger than those in WT mice, . There was also no clear differences in serum levels of nitric oxide, a cytotoxic effector molecule of activated macrophages, between WT and IFN-gamma R0/0 mice. There results suggest that mice can resisit aganinst cancer metastasis in the absense of IFN-gamma.