Conclusion
This study is the first to discover an anti-migratory potential of RV in EGF-activated VSMC that is most likely mediated via Rac1 inhibition.
Results
We show here that RV (50 μM) strongly reduces epidermal growth factor (EGF)- but not platelet-derived growth factor (PDGF)-induced VSMC migration using the wound-healing technique. Accordingly, RV inhibited Rac1 activation and lamellipodia formation in response to EGF but not PDGF as shown by pull-down assays and fluorescence microscopy after actin staining with phalloidin-FITC, respectively. Since Src-family kinases and the phosphatidylinositol-3 kinase (PI3K) are reported to be crucial upstream mediators of Rac1 activation we examined the PI3K inhibitor wortmannin and the src kinase inhibitor SU6656 side-by-side with RV for their anti-migratory potential. Whereas src inhibition abrogated both EGF- and PDGF-triggered migration, wortmannin, like RV, was more effective in EGF- than PDGF-activated cells, suggesting that PI3K inhibition, previously shown for RV in growth factor-activated VSMC, contributes to the anti-migratory effect of RV in EGF-stimulated VSMC.