The great majority of women diagnosed with epithelial ovarian cancer (EOC) will die of the disease. To date, the most significant results have come from advances in chemotherapy. There is considerable hope that novel biologically targeted therapy in combination with chemotherapy will improve survival. Bevacizumab, an antibody directed against the proangiogenic molecule vascular endothelial growth factor (VEGF) (Burger et al. 2005) shows great promise in ovarian cancer. There is little data, especially in human ovarian cancer cell lines, looking at how antiangiogenic agents and chemotherapy work together in combination. It is the specific purpose of this study to examine the growth inhibition that results from combination topotecan and bevacizumab in topotecan-resistant ovarian cancer cell lines that either did or did not express VEGF. To test the effect of chemotherapy on human ovarian cancer cells, seventeen ovarian cancer cell lines were treated with topotecan at different concentrations and time periods. Three pairs of these cell lines were further selected for assessing cell survival in the presence of bevacizumab alone or in combination with topotecan. Nine of seventeen cell lines showed resistant to topotecan treatment with a range of 62 to 100% cell survival. Three of these (OVCAR3; OVCAR5; SKOV3) have been previously shown to produce soluble VEGF (VEGF+). These cell lines were demonstrated relatively high resistance to 96-hours treatment with 0.3uM topotecan. When compared with a non-VEGF expressing cell line,A2780CP (VEGF-), VEGF+ cell lines (OVCAR3; OVCAR5; SKOV3) showed were significantly inhibited by bevacizumab when combined with topotecan after 24, 48 and 96 hours administration. This response was greater than the response to bevacizumab alone, suggesting synergy. This study demonstrates that topotecan resistant ovarian cancer cells that produce VEGF have a synergistic response to combination bevacizumab and topotecan. This opens further investigation into how other chemotherapeutics may behave when combined with antiangiogenic therapy in ovarian cancer.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]