蝎毒多肽提取物抑制H22肝癌血管生成的作用机制研究

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、P-Akt、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。

Study on the Mechanism of Polypeptide Extract from Scorpion Venom on Inhibition of Angiogene- sis of H22 Hepatoma

Objective To explore the mechanism of polypeptide extract from scorpion venom （PESV） on inhibiting angiogenesis. Methods The H22 hepatoma tumor model was established by subcutaneously implanting H22 hepatoma cells into mice. The tumor-bearing mice were randomly divided into 4 groups, i.e., the control group, the high dose PESV group, the low dose PESV group, and the 5-fluorouracil （5-Fu） group, 10 mice in each group. The intervention was lasted for 14 days. The growth curve of the tumor volume was drawn and the inhibition rate calculated. Pathological changes of the tumors were observed by HE staining. The microvessel density （MVD） was detected using SP method. The protein expression levels of phosphatidylinositol 3-kinase （ PI3K）, phosphoprotein kinase B （ P-Akt）, hypoxia-inducible factor-1α （HIF-1α）, and vascular endothelial growth factor-A （VEGF-A） were detected by immu- nohistochemical assay and Western blot. Results The tumor inhibitory rate was 64.8%, 43.7%, and 32.4% in the 5-Fu group, the high dose PESV group, and the low dose PESV group. Compared with the control group, the protein expression of PI3K, P-Akt, HIF-1α, and VEGF-A were obviously inhibited by PESV and 5-Fu （P 〈0.05 ,P 〈0.01 ）. The MVD also decreased in the high and low dose PESV groups （P 〈 0.05）. Conclusions PESV could inhibit the angiogenesis of H22 hepatoma. The mechanisms might be associated with suppressing the expression of PI3K, P-Akt, HIF-1α, and VEGF-A.