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[白藜芦醇对血管生成的抑制作用]

[Inhibitory effects of ampelopsin on angiogenesis].

作者信息

Luo Gao-qin, Zeng Sa, Liu De-yu

机构信息

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510089, China.

出版信息

Zhong Yao Cai. 2006 Feb;29(2):146-50.

Abstract

OBJECTIVE

To study the effect of ampelopsin on angiogenesis.

METHODS

The anti-angiogenic effect was evaluated by MTT assay for proliferation of endothelial cells. The concentration of vascular endothelial growth factor (VEGF) and basic-fibroblast growth factor (bFGF) from human hepatocellular carcinoma Bel-7402 cells were detected by enzyme linked immunosorbant assay (ELISA). Immunohistochemical staining was conducted to detect the expression of VEGF and bFGF. The VEGF and bFGF in the cancer cells were examined by flow cytometry. The inhibitory effect of ampelopsin on the growth of human hepatocellular carcinoma Bel-7402 in nude mice was studied.

RESULTS

Ampelopsin was shown to inhibit the proliferation of primary cultured bovine aortic endothelial cells in a concentration dependent manner in range of 6.4 - 51.2 microg/ml. The IC50 (50% inhibition concentration) value was 22.0 +/- 4.0 microg/ml. ELISA assay was shown that treatment with 12.8 microl/m1, 25.6 microl/ml and 38.4 microg/ml of ampelopsin resulted in an inhibition of VEGF production released by Bel-7402, and the inbibtitory rate was 14.2%, 40.0% and 49.6%, respectively. After exposure to 12.8 microg/ml of ampelopsin, a decrease in the expression and activity of VEGF and bFGF was observed by immunohistochemical staining. The concentration of VEGF and bFGF secretion by Bel-7402 cells were lower following ampelopsin treatment as shown by flow cytometry. Treatment with 25.6 microg/mL and 38.4 microg/ml of ampelopsin, the inbibitory rates were 32.2% and 57.4% for VEGF, and 54.9% and 62.6% for bFGF, respectively. The inhibitory rate of ampelopsin to the growth of the transplant tumor in nude mice were 24.3%, 41.4% and 45.75 respectively at the dose of 100 mg/kg, 150 mg/kg and 200 mg/kg.

CONCLUSION

Ampelopsin is a potent inhibitor of VEGF and bFGF expression and production in human hepatocellular carcinoma Bel-7402 cell, and may be a promising angiogenesis inhibitor.

摘要

目的

研究白藜芦醇对血管生成的影响。

方法

采用MTT法检测内皮细胞增殖以评估抗血管生成作用。通过酶联免疫吸附测定(ELISA)检测人肝癌Bel-7402细胞中血管内皮生长因子(VEGF)和碱性成纤维细胞生长因子(bFGF)的浓度。进行免疫组织化学染色以检测VEGF和bFGF的表达。通过流式细胞术检测癌细胞中的VEGF和bFGF。研究白藜芦醇对裸鼠人肝癌Bel-7402生长的抑制作用。

结果

白藜芦醇在6.4 - 51.2微克/毫升范围内呈浓度依赖性抑制原代培养的牛主动脉内皮细胞增殖。IC50(50%抑制浓度)值为22.0±4.0微克/毫升。ELISA检测显示,用12.8微升/毫升、25.6微升/毫升和38.4微克/毫升的白藜芦醇处理可抑制Bel-7402释放的VEGF产生,抑制率分别为14.2%、40.0%和49.6%。用12.8微克/毫升白藜芦醇处理后,免疫组织化学染色观察到VEGF和bFGF的表达及活性降低。流式细胞术显示,白藜芦醇处理后Bel-7402细胞分泌的VEGF和bFGF浓度降低。用25.6微克/毫升和38.4微克/毫升白藜芦醇处理时,VEGF的抑制率分别为32.2%和57.4%,bFGF的抑制率分别为54.9%和62.6%。在100毫克/千克、150毫克/千克和200毫克/千克剂量下,白藜芦醇对裸鼠移植瘤生长的抑制率分别为24.3%、41.4%和45.75%。

结论

白藜芦醇是一种有效的人肝癌Bel-7402细胞中VEGF和bFGF表达及产生的抑制剂,可能是一种有前景的血管生成抑制剂。

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