The Correlative Contribution Of VEGF And SDF-1/CXCR4 In Ovarian Cancer Cells Invasion And Proliferation

Objective:To investigate the effects of VEGF(vascular endothelial growth factor) on SDF-1 /CXCR4 mRNA expression and their correlative contribution among then on cell invasion and proliferation in human ovarian epithelial cancer cell line SKOV3, and then to try to find out some mechanism of SDF-1/CXCR4 signal in the development of ovarian cancer.Methods:The expression of SDF-1/CXCR4 mRNA before and after incubated with VEGF or anti-VEGF in human ovarian epithelial cancer cell line SKOV3 were evaluated by Real-time RT–PCR. The effects of VEGF, SDF-1, anti-VEGF and CXCR4 antagonist (AMD3100) on invasion of SKOV3 cells into Matrigel were measured using Transwell test(24-well format, 8.0-mm pore size with polycarbonate membrane). The cell growth rate of SKOV3 cell lines before and after incubated with VEGF, SDF-1, anti-VEGF and AMD3100 were determined using MTT(4-methyl thiazolyl tetrazolium)method.Results:(1) The expressions of SDF-1 and CXCR4 mRNA were up-regulated significantly by VEGF in a visible dose dependent manner.(2) Both VEGF and SDF-1 had a direct promotive effect on SKOV3 cell invasion. The effect of VEGF had a conspicuous dose dependent and can be blocked by anti-VEGF or AMD3100. The effect of SDF-1 had no evident dose dependent and can be blocked by AMD3100.(3) Both VEGF and SDF-1 had a direct promotive effect on SKOV3 cell proliferation. The effect of VEGF had some dose dependent and can be blocked by anti-VEGF but not by AMD3100. The effect of SDF-1 had no significant dose dependent and can be blocked by AMD3100.Conclusion:These results indicate that VEGF can up-regulate the expression of SDF-1 and CXCR4 mRNA, and both VEGF and SDF-1 have a direct promotive effect on cancer cells invasion and proliferation in human ovarian epithelial cancer cell line SKOV3.