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目的研究干扰素α(IFNα)对人肝细胞癌胸苷磷酸化酶(TP)表达水平及血管生成能力的影响。方法在体内外用一定剂量的IFNα处理人肝癌细胞SMMC7721,用RTPCR和ELISA方法分别检测细胞TPmRNA和蛋白表达水平,Boyden小室法检测诱导内皮细胞移动的能力,免疫组化法检测SMMC7721裸鼠皮下移植瘤组织中微血管密度(MVD)。结果IFNα上调SMMC7721细胞TPmRNA表达水平,呈现剂量依赖性。与未处理组相比,浓度为5000、10000U/ml的IFNα处理的细胞TPmRNA表达水平显著升高(P<0.05),但诱导内皮细胞移动的能力差异无统计学意义。随着IFNα剂量的增加,裸鼠皮下移植瘤组织中TP蛋白表达水平逐渐增加,而MVD数目先增加后下降。IFNα不同剂量时(9.0×106、1.5×107U·kg-1·d-1),肿瘤组织中TP蛋白表达水平显著高于(48ng/mg±24ng/mg)未处理组(60ng/mg±6ng/mg,P<0.01);MVD数目分别为6.0±1.8,4.0±1.5,P<0.05)。与未处理组相比IFNα(1.5×107U·kg-1·d-1)组肿瘤重量明显下降(P<0.05)。结论一定剂量的IFNα既能上调肝细胞癌TP表达水平,又能抵消TP表达上调后促进血管生成能力的增强。
Objective To investigate the effects of interferon α (IFNα) on the expression of thymidine phosphorylase (TP) and angiogenesis in human hepatocellular carcinoma. Methods Human hepatocellular carcinoma SMMC7721 cells were treated with IFNα in vitro and in vivo. The expressions of TP mRNA and protein were detected by RTPCR and ELISA respectively. The ability of endothelial cells was detected by Boyden chamber assay. The subcutaneous xenografts of nude mice were detected by immunohistochemistry. Tissue microvessel density (MVD). Results IFNα up-regulated the expression of TP mRNA in SMMC7721 cells in a dose-dependent manner. Compared with the untreated group, the expression of TP mRNA in IFNα-treated cells at 5000 and 10000U / ml was significantly increased (P <0.05), but there was no significant difference in the ability to induce endothelial cell migration. With the increase of IFNα dose, the expression of TP protein gradually increased in subcutaneously transplanted tumor tissue of nude mice, while the number of MVD first increased and then decreased. The levels of TP protein in tumor tissue were significantly higher than those in the untreated group (60ng / mg ± 6ng) at different doses of IFNα (9.0 × 106,1.5 × 107U · kg-1 · d-1) / mg, P <0.01); the number of MVDs was 6.0 ± 1.8, 4.0 ± 1.5, P <0.05). Compared with untreated group, tumor weight of IFNα (1.5 × 107U · kg-1 · d-1) group decreased significantly (P <0.05). Conclusion A certain dose of IFNα can upregulate the expression of TP in hepatocellular carcinoma and up-regulate the expression of TP, which can promote the enhancement of angiogenesis.