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目的探讨雷帕霉素对人肝癌裸鼠皮下移植瘤生长的影响及机制。方法建立人肝癌裸鼠皮下移植瘤模型24只,随机分为对照组、RAPA 小剂量组(每日1 mg/kg 体重)、RAPA 大剂量组(每日5 mg/kg 体重)。用药4周后观察肿瘤体积和重量、肿瘤组织切片行透射电镜检查、荧光定量聚合酶链反应(PCR)法检测肿瘤的血管内皮生长因子(VEGF)、基质金属蛋白酶2(MMP-2)mRNA 的表达,酶联免疫吸附试验(ELISA)法测定裸鼠血 VEGF、MMP-2浓度。结果与对照组比较,雷帕霉素小剂量组和大剂量组均能抑制肿瘤生长[(0.42±0.17)cm~3和(0.38±0.21)cm~3比(0.78±0.25)cm~3,P<0.05];VEGF mRNA、MMP-2 mRNA 的转录和翻译显著减少(P<0.01)。结论雷帕霉素可以通过抑制肝癌细胞 VEGF 和 MMP-2的 mRNA 转录和蛋白表达,抑制肿瘤生长,但不呈剂量依赖性。
Objective To investigate the effect of rapamycin on the growth of human hepatocellular carcinoma xenograft in nude mice and its mechanism. Methods Twenty-four human hepatocellular carcinoma xenografts in nude mice were established and randomly divided into control group, low dose RAPA group (1 mg / kg body weight daily) and high dose RAPA group (5 mg / kg body weight daily). Tumor volume and weight were observed after 4 weeks of treatment. Tumor tissue sections were examined by transmission electron microscopy. The expression of VEGF, MMP-2 mRNA was detected by fluorescence quantitative polymerase chain reaction (PCR) Expression of VEGF and MMP-2 in nude mice were determined by enzyme linked immunosorbent assay (ELISA). Results Compared with the control group, both low dose rapamycin and high dose rapamycin inhibited the tumor growth [(0.42 ± 0.17) cm ~ (3) and 0.38 ± 0.21 cm ~ 3 (0.78 ± 0.25) cm ~ P <0.05]. The transcription and translation of VEGF mRNA and MMP-2 mRNA were significantly decreased (P <0.01). Conclusion Rapamycin can inhibit tumor growth by inhibiting mRNA and protein expression of VEGF and MMP-2 in hepatoma cells, but not in a dose-dependent manner.