α干扰素和环氧合酶2抑制剂对裸鼠肝癌移植瘤生长和肿瘤血管生成的抑制作用

Inhibitory effects of cyclooxygenase-2 inhibitor and or-interferon on growth of human liver cancer xenografts and tumor angiogenesis in nude mice

目的探讨仪干扰素α（α interfern，α—IFN）和环氧合酶-2抑制剂（celecoxib）对人肝癌SMMC-7721裸鼠移植瘤生长和肿瘤血管生成是否具协同抑制作用。方法根据用药不同，48只裸鼠分为4组，α-IFN＋celecoxib组，α—IFN组，celecoxib组和对照组。观察celecoxib及旺-IFN对裸鼠移植瘤的体积和质量的影响。采用免疫组化和RT—PCR法检测裸鼠移植瘤组织中血管内皮生长因子（vascular endothelial growth factor，VEGF）和Cox-2的表达，检测celecoxib和α—IFN对微血管密度（microvessel density，MVD）的作用。结果对照组肿瘤呈递增性生长，其他3个治疗组肿瘤生长明显受抑制，其中celecoxib＋α-IFN组移植瘤体积和质量最小，抑瘤效果最好，抑瘤率是61．84％。免疫组化检测显示，3个治疗组中celecoxib＋α-IFN组抑制VEGF和MVD的效果最好，差异有统计学意义（P〈0．01）。RT—PCR检测显示，celecoxibα-IFN组与α-IFN组、celecoxib组与对照组比较，COX-2和VEGFmRNA表达水平均明显减弱分别（P〈0．01）。结论环氧合酶-2抑制剂celecoxib和α-IFN对人肝细胞癌SMMC-7721细胞裸小鼠移植瘤的生长和血管生成有协同抑制作用。

Objective To investigate α-interferon （ α-IFN ） and cyclooxygenase-2 （ COX-2 ） inhibitor celecoxib synergistically inhibit the growth of human liver cancer SMMC-7721 cells xenografts and tumor angiogencsis in a nude mouse model. Methods The effects of celecoxib and a-interferon on tumor volumes and weight were observed. The expressions of VEGF and Cox-2 were determined by immunohistochemistry and RT-PCR, and the effect of α-interferon on MVD also was observed by immunohisto chemistry. Results During the period of observation tumor volume increased progressively in control group, while it was suppressed obviously in other drug treatment groups. The average tumor volume was significantly smaller in celecoxib ＋ α-IFN group than that in IFN group, celecoxib group and control group（P 〈 0. 01, respectively）, its inhibitory rate was 61.84%. Immunohistochemistry showes that the VEGF and MVD was significantly smaller in celecoxib ＋ IFN group than that in α-IFN group, celecoxib group and control group （P 〈0. 01, respectively）. RT-PCR shows that the COX-2mRNA and VEGF mRNA pression was lower in the celecoxib ＋ α-IFN group than in α-IFN group, celeeoxib group and control group （ P 〈 0. 01 ）. Conclusions The COX-2 inhibitor eelecoxib and α-interferon synergistically reduces xenografts growth of human liver cancer SMMC-7721 ceils effectively via suppressing tumor growth and angiogenesis.