Hu Xin-Xin, Zhang Qin-Hua, Qi Cong
Department of Gynecology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2012 Jul;32(7):970-4.
To investigate the anti-angiogenic effects and mechanisms of Zengmian Yiliu Granule (ZMYLG) on ovarian carcinoma xenograft.
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-1alpha (HIF-1alpha) in the tumor were determined using immunohistochemical assay and RT-PCR.
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-1alpha (P < 0.01, P < 0.05).
ZMYLG could inhibit neogenesis of tumor vessels. Its mechanisms might be associated with down-regulating the expression of HIF-1alpha, modifying the hypoxic state, inhibiting the expressions of VEGF and FLK-1, and exerting its anti-angiogenic effects.
探讨增免抑瘤颗粒(ZMYLG)对卵巢癌移植瘤的抗血管生成作用及其机制。
建立SKOV3卵巢癌荷瘤小鼠模型。将荷瘤小鼠随机分为对照组、紫杉醇组、ZMYLG高、中、低剂量组,每组8只。给药持续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的方法计算移植瘤中的微血管密度(MVD)。采用免疫组化法和RT-PCR法检测肿瘤中血管内皮生长因子(VEGF)及其受体胎儿肝激酶-1(FLK-1)、缺氧诱导因子-1α(HIF-1α)的蛋白和mRNA表达。
紫杉醇组、ZMYLG高、中、低剂量组卵巢癌移植瘤的MVD明显降低,与对照组比较差异有统计学意义(P<0.01,P<0.05)。各ZMYLG剂量组均可下调VEGF、FLK-1和HIF-1α的蛋白和mRNA表达(P<0.01,P<0.05)。
ZMYLG可抑制肿瘤血管新生。其机制可能与下调HIF-1α表达、改善缺氧状态、抑制VEGF和FLK-1表达并发挥抗血管生成作用有关。