Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 28, 2011; 17(44): 4875-4882
Published online Nov 28, 2011. doi: 10.3748/wjg.v17.i44.4875
Inhibition of tumor angiogenesis by TTF1 from extract of herbal medicine
Chao Liu, Xiao-Wan Li, Li-Min Cui, Liang-Chang Li, Li-Yan Chen, Xue-Wu Zhang
Chao Liu, Xiao-Wan Li, Liang-Chang Li, Li-Yan Chen, Xue-Wu Zhang, Basic Medical College, Yanbian University, Yanji 133002, Jilin Province, China
Chao Liu, Li-Min Cui, Clinical Medical College, Yanbian University, Yanji 133002, Jilin Province, China
Author contributions: Liu C constructed the chick embryo chorioallantoic membrane model; Liu C and Li XW constructed the BALB/c nude mouse model, and measured the molecular biology parameters; Cui LM performed drug extraction and separation; Li LC and Chen LY measured immunohistochemical parameters; Zhang XW designed the project, analyzed the data and wrote the manuscript.
Supported by The National Natural Science Foundation Grant, No. 30860374
Correspondence to: Xue-Wu Zhang, Professor, Basic Medical College, Yanbian University, Yanji 133002, Jilin Province, China. zhangxuewu@ybu.edu.cn
Telephone: +86-433-2435102 Fax: +86-433-2435104
Received: August 11, 2011
Revised: October 12, 2011
Accepted: November 4, 2011
Published online: November 28, 2011
Abstract

AIM: To study the inhibition of tumor angiogenesis by 5,2,4´-trihydroxy-6,7,5´-trimethoxyflavone (TTF1) isolated from an extract of herbal medicine Sorbaria sorbifolia.

METHODS: Angiogenic activity was assayed using the chick embryo chorioallantoic membrane (CAM) method. Microvessel density (MVD) was determined by staining tissue sections immunohistochemically for CD34 using the Weidner capillary counting method. The mRNA and protein levels of vascular endothelial growth factor (VEGF), vascular endothelialgrowth factor receptor 2 (VEGFR2, Flk-1/KDR), basic fibroblast growth factor (bFGF), cyclo-oxygenase (COX)-2 and hypoxia-inducible factor (HIF)-1α were detected by quantitative real-time polymerase chain reaction and Western blotting analysis.

RESULTS: The TTF1 inhibition rates for CAM were 30.8%, 38.2% and 47.5% with treatment concentrations of 25, 50 and 100 μg/embryo × 5 d, respectively. The inhibitory rates for tumor size were 43.8%, 49.4% and 59.6% at TTF1 treatment concentrations of 5, 10, and 20 μmol/kg, respectively. The average MVD was 14.2, 11.2 and 8.5 at treatment concentrations of 5 μmol/kg, 10 μmol/kg and 20 μmol/kg TTF1, respectively. The mRNA and protein levels of VEGF, KDR, bFGF, COX-2 and HIF-1α in mice treated with TTF1 were significantly decreased.

CONCLUSION: TTF1 can inhibit tumor angiogenesis, and the mechanism may be associated with the down-regulation of VEGF, KDR, bFGF, HIF-1α and COX-2.

Keywords: Chinese herbal medicine; Sorbaria sorbifolia; TTF1; Inhibition; Tumor angiogenesis