Silencing of VEGFR-2 by RNA interference in an epithelial ovarian cancer cell line reduced LPA-induced invasion

A73

Our previous studies have shown that VEGF could induce epithelial ovarian cancer (EOC) invasion and migration in an MMP-dependent manner and that inhibition of VEGF receptor 2 (VEGFR-2) by SU1498 could suppress VEGF and LPA-induced EOC invasion and migration. However, the expression profiles of VEGF and VEGFRs in EOC remain unclear. In the present study, we examined the expression of VEGFR-1, VEGFR-2, and co-receptors NRP-1 and NRP-2 in established EOC cells lines (DOV13, R182, OVCA429) as well as in an immortalized normal ovarian epithelium (IOSE-29). We also examined the expression of two VEGF isoforms, VEGF₁₂₁ and VEGF₁₆₅, in those cell lines and assessed the effect of LPA on VEGF and VEGFR expression. Our results showed that the VEGFR-2 expression correlated with tumor cell invasiveness and LPA, at 10-80 μmol/L (μM), remarkably induced VEGFR-2 expression (P<0.05), without significantly affecting VEGFR-1 expression. LPA (1 μM) also significantly induced the expression of VEGF₁₂₁ (P<0.001)and VEGF₁₆₅ (P<0.01). However, only VEGF₁₂₁ expression is induced by higher concentration of LPA (40-80 μM). By small interference RNA (siRNA) transfection, we demonstrated that inhibition of VEGFR-2 expression could significantly decrease DOV13 cells’ invasiveness (P<0.001). Moreover, silencing of VEGFR-2 by siRNA significantly suppressed LPA-induced DOV13 invasion. These results suggest that knocking down VEGFR-2 expression by RNAi may be an effective strategy to inhibit ovarian cancer metastasis.