不同剂量IFN-γ体内对小鼠H22肝癌发生发展的作用研究  

Effect of different doses of IFN-γ on the development of mouse H22 hepatoma

作　　者：贺宇飞[1] 张桂梅[1] 张慧[1] 陈洪涛[1] 冯作化[1] 

机构地区：[1]华中科技大学同济医学院生化与分子生物学系,武汉430030

出　　处：《中华微生物学和免疫学杂志》2005年第4期292-296,共5页Chinese Journal of Microbiology and Immunology

基　　金：国家重点基础研究发展 (973 )计划 (2 0 0 2CB5 13 10 0 )

摘　　要：目的　探讨不同剂量尤其是低剂量的γ干扰素(IFN γ)体内表达对小鼠H2 2肝癌发生发展的影响。方法　利用小鼠H2 2肝癌体内发生和进展的模型,以不同剂量IFN γ表达质粒(mIFNG)进行长期和短期直接肌肉转染,检测H2 2肝癌的发生率及生长速率;半定量RT PCR、ELISA及实时定量PCR检测IFN -γ的表达情况;肌肉转染表达IFN -γ阻断剂,检测其对IFN -γ作用的影响。结果　注射低剂量(10 μg)的mIFNG质粒局部持续表达IFN γ可明显促进小鼠H2 2肝癌的发生和发展,然而短暂的表达则没有这种促进作用。IFN -γ拮抗剂则可对抗低剂量表达IFN -γ对肿瘤的促进作用。另一方面,注射高剂量(10 0 μg)的mIFNG质粒局部持续表达IFN -γ则能够介导明显的抗肿瘤效应。结论IFN γ对小鼠H2 2肝癌具有双重作用,也可能是联系慢性炎症与肿瘤发生发展之间的一个十分重要的衔接者。Objective To investigate in vivo effect of different doses, especially low dose of IFN-γ on the development of mouse H22 hepatoma. Methods Based on the tumor growth and progression models of mouse H22 hepatoma, effects of long- and short-term expression of IFN-γ on the incidence and growth of H22 hepatoma were observed after exposure to different doses of IFN-γ. Expression plasmid (mIFNG) were transfected directly into mouse muscle. Semi-quantitative RT-PCR, ELISA and real-time PCR were used to detect the expression of IFN-γ after transfection. Results Sustained low-level expression of IFN-γ significantly promoted H22 tumor development after injection of mIFNG plasmid with dosage 10?μg×8. Sustained expression of IFN-γ blockade could inhibit the tumor-promoting effect of IFN-γ. However, transitory expression of IFN-γ did not have such effect when mice were injected twice with 10?μg of mIFNG plasmid. On the other hand, sustained high-level expression of IFN-γ mediates significant antitumor effect when mice received 100?μg of mIFNG plasmid injections for 8 times. Conclusion Our results suggest that IFN-γ functions as a 'double-edged sword' in mouse H22 tumor development and may function as an important shifting mechanism from chronic inflammation to tumor development.

关 键 词：IFN-Γ H22肝癌 发生发展 不同剂量 小鼠 作用研究 半定量RT-PCR 定量PCR检测 ELISA 抗肿瘤效应 体内表达 γ干扰素 表达质粒 生长速率 表达情况 双重作用 慢性炎症 低剂量 发生率 阻断剂 拮抗剂 高剂量 转染 肌肉 局部 

分 类 号：R735.7[医药卫生—肿瘤]