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目的探讨蝎毒多肽提取物抗肿瘤血管生成的机制。方法建立H22肝癌皮下荷瘤模型,随机分为荷瘤对照组(对照组),蝎毒多肽提取物(polypeptide extract from scorpion venom,PESV)高、低剂量组,5-氟尿嘧啶(5-fluorouracil,5-Fu)组,每组10只。连续干预14天。绘制肿瘤体积生长曲线并计算抑瘤率;HE染色观察各组肿瘤组织病理变化;采用SP法检测各组肿瘤组织微血管密度(microvessel density,MVD)。采用免疫组织化学法及Western blot法检测各组磷脂酰肌醇-3-激酶(phosphatidylinositol 3-kinase,PI3K)、磷酸化蛋白激酶B(phosphoprotein kinase B,P-Akt)、缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)、血管内皮生长因子-A(vascular endothelial growth factor-A,VEGF-A)蛋白表达。结果5-Fu组,PESV高、低剂量组抑瘤率分别为64.8%、43.7%和32.4%。与对照组比较,三个给药组PI3K、PAkt、HIF-1α、VEGF-A蛋白表达明显下调(P<0.05,P<0.01),PESV高、低剂量组MVD均降低(P<0.05)。结论 PESV可抑制H22肝癌血管生成,其机制可能与抑制肿瘤微环境中PI3K、P-Akt、HIF-1α、VEGF-A的表达有关。
Objective To explore the anti-tumor angiogenesis mechanism of scorpion venom peptide extract. Methods H22 hepatocellular carcinoma subcutaneous tumor model was established and randomly divided into tumor-bearing control group (control group), polypeptide extract from scorpion venom (PESV) high and low dose group, 5-fluorouracil -Fu) group, 10 in each group. Continuous intervention for 14 days. The tumor volume growth curve was drawn and the tumor inhibition rate was calculated. The histopathological changes of the tumor tissues were observed by HE staining. The microvessel density (MVD) of the tumor tissues was detected by SP method. The expressions of phosphatidylinositol 3-kinase (PI3K), phosphorylated kinase B (P-Akt), hypoxia-inducible factor-1α (hypoxia-inducible factor-1α, HIF-1α) and vascular endothelial growth factor-A (VEGF-A) Results The inhibition rates of 5-Fu group and PESV high and low dose groups were 64.8%, 43.7% and 32.4%, respectively. Compared with the control group, the expressions of PI3K, PAkt, HIF-1α and VEGF-A in the three groups were significantly decreased (P <0.05, P <0.01), while those in the PESV group were lower (P <0.05). Conclusions PESV can inhibit the angiogenesis of H22 hepatocellular carcinoma. The mechanism may be related to the inhibition of the expression of PI3K, P-Akt, HIF-1α and VEGF-A in tumor microenvironment.