干扰素-α抑制高转移潜能人肝癌裸鼠肝细胞生长因子及血管内皮生长因子的表达

Interferon-α significantly inhibits the hepatocyte growth factor and vascular endothelial growth factor expression in the hepatocellular carcinoma of nude mice model with highly metastatic potential

目的 观察干扰素-α（IFN-α）对高转移潜能人肝癌裸鼠模型中血管内皮生长因子（VEGF）、肝细胞生长因子（HGF）mRNA表达的影响.方法 应用绿色荧光蛋白转染的人高转移肝癌细胞株HCC-LM3建立高转移潜能人肝癌裸鼠模型LCI-D20,种植后第2天开始分别使用IFN-α 1.5×104 U/（kg·d）（治疗组,n=12）或生理盐水（对照组,n=12）皮下注射,28 d后处死裸鼠,比较肝脏肿瘤的大小和肝内转移,免疫组织化学检测肿瘤微血管密度（MVD）,实时荧光定量聚合酶链反应（PCR）检测肿瘤HGF和VEGF表达的变化.结果治疗组、对照组的肝内肿瘤大小分别为（0.11±0.03）cm3、（0.99±0.37）cm3（P〈0.05）;肝内转移率分别为33.3%（4/12）、83.3%（10/12）（P〈0.05）;肝内转移数目分别为0.67±0.31个比1.91±0.43个（P〈0.05）;肿瘤内MVD分别为3.19±0.52、4.85±0.72（P〈0.05）;肿瘤VEGF mRNA表达（-△CT）分别为-8.16±0.54、-6.95±0.86（P〈0.05）;HGF mRNA表达分别为-11.62±0.63、-10.56±0.48（P〈0.05）.结论 IFN-α对HGF及VEGF表达的抑制可能是其抗肿瘤血管生成作用、抑制肿瘤生长转移作用的机制之一.

Objective To investigate the inhibitory effect of interferon （ IFN ）-α on the hepatocyte growth factor （HGF） and vascular endothelial growth factor （VEGF） expression in nude mice orthotopically transplanted with human hepatocelllular carcinoma with highly metastatic potential.Methods A nude mice model with highly metastatic potential （LCI-D20） was established with HCC-LM3 transfected withgreen-fluorescent protein （GFP） gene in nude mice,One day after transplantation,nude mice were divided mal saline in control group,respectively.After 28 days,nude mice were sacrificed,the volume of tumor and intrahepatic metastases in two groups were compared.The microvessel density （MVD） of tumor was observed by immunohistochemistry.The expression of VEGF and HGF in tumor was detected by real-time reverse transcription-polymerase chain reaction （RT-PCR）.Results The tumor sizes in treatment group and control group was （0.11 ± 0.03 ） and （ 0.99 ± 0.37） cm3,respectively （ P 〈 0.05 ）.The metastasis rate in treatment group and control group was 33.3% （4/12） and 83.3% （ 10/12）,respectively （P〈0.05 ）.The average number of metastatic nodules in treatment group and control group was 0.67 ± 0.31 and 1.91 ±0.43,respectively （ P 〈 0.05 ）.Intratumoral MVD in treatment group and control group was 3.19 ±0.52 and 4.85 ± 0.72,respectively （P 〈 0.05 ）.The VEGF expression （ -△CT） in treatment group and control group was -8.16 ±0.54 and -6.95 ±0.86,respectively （P〈0.05）.The HGF expression in treatment group and control group was -11.62 ± 0.63 and - 10.56 ±0.48,respectively （ P 〈0.05）.Conclusion IFN-α significantly inhibit growth of tumor and intrahepatic invasion HCC-LM3 xengraft modelas well as intratumoral MVD which might contribute to inhibition of VEGF and HGF expression by IFN-α.