增免抑瘤颗粒剂抗卵巢癌荷瘤小鼠皮下移植瘤血管生成作用的实验研究

作者	单位
胡欣欣	上海中医药大学附属曙光医院妇科
张勤华	上海中医药大学附属曙光医院妇科
齐聪	上海中医药大学附属曙光医院妇科
李久现	上海中医药大学附属曙光医院妇科

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中文摘要:

目的探讨增免抑瘤颗粒剂(Zengmian Yiliu Granule,ZMYLG)抗SKOV3卵巢癌荷瘤小鼠皮下移植瘤血管生成的影响及机制。方法建立SKOV3卵巢癌荷瘤小鼠模型,随机分为对照组、紫杉醇组、ZMYLG高、中、低剂量组(简称ZMYLG高、中、低组),每组8只,连续给药10天。采用细胞膜分化抗原34(CD34)抗体标记新生血管内皮细胞法,计算皮下移植瘤内微血管密度(MVD);免疫组化法、RT-PCR法检测皮下移植瘤内血管内皮生长因子(VEGF)及其受体胎肝激酶-1(FLK-1)、缺氧诱导因子(HIF-1α)蛋白及mRNA表达水平。结果与对照组比较,紫杉醇组和ZMYLG高、中、低剂量组移植瘤内MVD明显降低,差异有统计学意义(P<0.01,P<0.05)。ZMYLG各剂量组均能下调瘤组织中VEGF、FLK-1及HIF-1α蛋白及mRNA表达量(P<0.01,P<0.05)。结论 ZMYLG能抑制肿瘤血管新生,其机制可能与下调HIF-1α表达,改善荷瘤小鼠缺氧状态,抑制VEGF及其受体FLK-1表达,发挥抗肿瘤血管生成作用有关。

英文摘要:

Objective To investigate the anti-angiogenic effects and mechanisms of Zengmian Yiliu Granule(ZMYLG) on ovarian carcinoma xenograft.Methods The SKOV3 ovarian carcinoma bearing mouse model was established.The tumor-bearing mice were randomly divided into the control group,the paclitaxel group,the high,medium,and low dose ZMYLG group,8 in each group.The medication was lasted for ten days.The microvessel density(MVD) in the xenograft was calculated by the method of using cell membrane differentiation antigen 34(CD34) antibody marking new vascular endothelial cells.The protein and mRNA expressions of vascular endothelial growth factor(VEGF)and its receptor fetal liver kinase-1(FLK-1),hypoxia inducible factor-1α(HIF-1α) in the tumor were determined using immunohistochemical assay and RT-PCR.Results The MVD of ovarian carcinoma xenografts in the paclitaxel group,the high,medium,and low dose ZMYLG group obviously decreased,showing statistical difference when compared with the control group(P<0.01,P<0.05).Each ZMYLG dose group could down-regulate the protein and mRNA expressions of VEGF,FLK-1,and HIF-1α(P<0.01,P<0.05).Conclusions ZMYLG could inhibit neogenesis of tumor vessels.Its mechanisms might be associated with down-regulating the expression of HIF-1α,modifying the hypoxic state,inhibiting the expressions of VEGF and FLK-1,and exerting its anti-angiogenic effects.

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