Development of molecular target therapy to VEGF and VEGFR against oral cancer with RNAi methods

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Cell migration plays a significant role in cancer invasion and metastasis. Our previous studies have shown vascular endothelial growth factor ( VEGF) and VEGF receptor 1 ( Flt-1 ) express in oral squamous cell carcinoma ( SCC ) cells. These finding suggests VEGF-VEGFR system might regulate in autocrine manner as well as angiogenesis in paracrine manner.In this study, we examined the expression of VEGF and VEGFR in melanoma cells. The participation of VEGF and VEGFR in invasion and metastasis of melanoma cells was also investigated.VEGF-induced proliferation of melanoma cells were suppressed by VEGFR-1 antisense oligo, but not by VEGFR-2 antisense oligo.Checkerbord analysis showed that VEGF induced Chemotaxitic and Chemokinetic migration in melanoma cells. The VEGF-induced migration was inhibited by VEGFR tyrosine kinase inhibitor. The migration was suppressed by VEGFR-1 antisense oligo, but not by VEGFR-2 antisense oligo.VEGF induced phosphorilation of Akt. PI3 kinase inhibitor block the VEGF-induced phosphorilation of PI3/Akt kinase cascade, and suppressed VEGF-induced motility of melanoma cells. These findings suggest that migration of melanoma cells is regulated with VEGF-induced activation of PI3/Akt kinase cascade