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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Silibinin inhibits angiogenesis via Flt-1, but not KDR, receptor up-regulation.

BACKGROUND: Our previous study found that silymarin (SM) and its major pure component silibinin (SB) have anti-angiogenic effects via decreased vascular endothelium growth factor ( VEGF) secretion of LoVo cells (colon cancer). We designed this consecutive study to evaluate the anti-angiogenic effects of SM/SB in vivo, and on VEGF receptor ( VEGFR) gene expression. MATERIALS AND METHODS: We used LoVo cells exposed to SM/SB in a modified chicken chorioallantoic membrane assay (CAM) to evaluate anti-angiogenic effects. We used EA.hy 926 cells (endothelial cells) exposed to SM/SB to evaluate the effect on VEGFR-1 (Flt-1) and VEGFR-2 (KDR), with 1-step, real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: In CAM, SM/SB showed a dose-dependent decrease on the vascular density index (VDI) induced by LoVo cells, as did thalidomide in a concentration of 10 microg/ml. Adding escalating dosages of VEGF successfully reversed this inhibitory effect. RT-PCR revealed that SB up-regulated Flt-1 mRNA expression of EA.hy 926 cells. SM had a similar trend, although the effect was not statistically significant (P = 0.19). Neither drug effected KDR mRNA expression. CONCLUSION: We conclude that anti-angiogenic effects of SM/SB are associated with the up-regulation of VEGFR-1 (Flt-1) gene expression and that they are good candidates for combination therapy to treat colorectal cancer.[1]


  1. Silibinin inhibits angiogenesis via Flt-1, but not KDR, receptor up-regulation. Yang, S.H., Lin, J.K., Huang, C.J., Chen, W.S., Li, S.Y., Chiu, J.H. J. Surg. Res. (2005) [Pubmed]
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