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首页> 外文期刊>World Journal of Gastroenterology >Fumagillin treatment of hepatocellular carcinoma in rats: an in vivo study of antiangiogenesis.
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Fumagillin treatment of hepatocellular carcinoma in rats: an in vivo study of antiangiogenesis.

机译：烟曲霉素治疗大鼠肝细胞癌：体内抗血管生成研究。

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AIM: To investigate the effect and possible mechanisms of antiangiogenesis therapy for HCC in rats. METHODS: Adult male LEW/SsN rats were divided into 3 groups, 25 animals each. Group A was the control group. Groups B and C were given diethylnitrosamine, 5 mg/kg/d. In addition, group C rats received an intraperitoneal injection of fumagillin, 30 mg/(kg x d). Five animals in each group were killed at 6th, 12th, 18th, 20th and 24th wk to evaluate the development of HCC and metastasis. Weight of the rats, liver tumors, and number of organs involved by HCC were measured at each stage. We compared methionine aminopeptidase-2 (MetAP-2) mRNA, Bcl-2 mRNA, telomerase mRNA, and telomerase activity at 24th wk in the liver tissue of group A rats and tumor tissue of HCC from group B and C rats. RESULTS: No HCC developed in group A, but tumors were present in group B and C rats by the 18th wk. At wk 20 and 24, the median liver weight in group B was 0.64 g (range: 0.58-0.70 g) and 0.79 g (range: 0.70-0.90 g) (P = 0.04), and that in group C was 0.37 g (range: 0.35-0.42 g) and 0.39 g (range: 0.35-0.47 g) (P = 0.67). The liver weight in group C rats was significantly lower than that in group B rats (P = 0.009). At the same time, the median metastasis score (number of organ systems involved) was 3 (range2-3) in group B, and 1 (range 1-2) in group C, a significant difference between the groups (P = 0.007, 0.004). The levels of MetAP-2 mRNA were significantly higher in groups B and C than in group A (P = 0.025), and significantly higher in group C than in group B (P = 0.047). The level of Bcl-2 mRNA was significantly higher in group B than in group A (P = 0.024), but lower in group C than in group B, although not significantly (P = 0.072). Telomerase mRNA was significantly higher in group B than in group A (P = 0.025), but significantly lower in group C than in group B (P = 0.016). The same inter-group relationship was also true for telomerase activity (P = 0.025 and 0.046). CONCLUSION: Fumagillin effectively inhibits both liver tumor growth and metastasis in rats in vivo. A possible mechanism is fumagillin-induced inhibition of MetAP-2, which plays an essential role in endothelial cell proliferation. Inhibition of MetAP-2 also results in inhibition of Bcl-2 and telomerase activity.
机译：目的：探讨抗血管生成治疗肝癌的作用及其可能机制。方法：成年雄性LEW / SsN大鼠分为3组，每组25只。 A组为对照组。 B组和C组分别给予5 mg / kg / d的二乙基亚硝胺。另外，C组大鼠腹膜内注射烟曲霉素30 mg /（kg x d）。每组五只动物分别在第6、12、18、20和24周被处死，以评估HCC的发展和转移。在每个阶段测量大鼠的体重，肝肿瘤和肝癌累及的器官数量。我们比较甲硫氨酸氨基肽酶2（MetAP-2）mRNA，Bcl-2 mRNA，端粒酶mRNA和端粒酶活性在第24周时在A组大鼠的肝组织以及B和C组HCC的肿瘤组织中的作用。结果：第18周时，A组未发生肝癌，但B和C组大鼠均出现肿瘤。在第20周和第24周，B组的平均肝重为0.64 g（范围：0.58-0.70 g）和0.79 g（范围：0.70-0.90 g）（P = 0.04），而C组的中位肝脏重量为0.37 g（范围：0.04）。范围：0.35-0.42 g）和0.39 g（范围：0.35-0.47 g）（P = 0.67）。 C组大鼠的肝脏重量显着低于B组大鼠（P = 0.009）。同时，B组的中位转移评分（涉及的器官系统数）为3（范围2-3），C组为1（范围1-2），两组之间存在显着差异（P = 0.007， 0.004）。 B组和C组MetAP-2 mRNA的水平显着高于A组（P = 0.025），C组显着高于B组（P = 0.047）。 B组中Bcl-2 mRNA的水平显着高于A组（P = 0.024），而C组中Bcl-2 mRNA的水平则低于B组，尽管不显着（P = 0.072）。 B组端粒酶mRNA显着高于A组（P = 0.025），但C组显着低于B组（P = 0.016）。端粒酶活性也存在相同的组间关系（P = 0.025和0.046）。结论：富马西林可有效抑制大鼠体内肝肿瘤的生长和转移。可能的机制是福马洁林诱导的MetAP-2抑制，其在内皮细胞增殖中起重要作用。 MetAP-2的抑制也导致Bcl-2和端粒酶活性的抑制。

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