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- W2231516854 abstract "AACR Annual Meeting-- Apr 18-22, 2009; Denver, COSolid tumors often develop an angiogenic phenotype that promotes the establishment of an expanding vascular network for delivery of oxygen and other nutrients. The tumor vasculature is an established target for the therapy of solid tumor. Agents designed to prevent new vessel formation as antiangiogenic agent, or to damage existing vessels, as vascular disrupting agent(VDA), have been developed and have shown efficacy in preclinical model, and in clinical studies. For pharmacodynamic study of vascular inhibitor and dual action-chemotherapeutic agent in vitro culture model, recapitulating interaction between tumor cell and endothelial cell, is better in terms of clinical relevancy. In this study, we developed a tumor-endothelium coculture model using human colorectal, cervix and head & neck cancer cells (HT-29, DLD-1, SiHa, HeLa and PCI-1) and HUVECs. HUVECs were cultured for 1day to confirm tube formation and stained with a cell tracker(CMFDA) before coculturing with tumor cells for 1 day. Cells were stained with PI after drug treatment and viability was accessed by dual-fluorescence microscopy and image analysis. Three dimensional cocultures were well established with DLD-1 and HT-29 cells with preserved tube formation of HUVECs. SiHa and HeLa cells were incompatible with HUVECs, resulting in cell death of HUVECs. PCI-1 cells did not suppress the growth of HUVECs, however, tube formation was not sustained. We also evaluated the pharmacodynamics of chemotherapeutic agents including paclitaxel, CPT-11 and arsenic compounds. Paclitaxel and CTP-11 showed inhibition on only tumor cells but arsenic compounds affected on both cell types. The dual action of arsenic compound showed 10 fold different level of cytotoxicity between tube formation of HUVECs and growth of tumor cells (0.1#956;M vs 1#956;M). The IC50 of arsenic compounds in the HUVECs increased 35 fold under co-culture condition and when cultured in condition media of HT-29 increased.These results indicate that HUVECs can be cocultured into 3-dimention structure with specific solid tumor cell lines. This in vitro coculture model, of endothelial cells and tumor cells, can be successfully used for investigation of pharmacodynamic study of vascular targeting and dual-action chemotherapeutic agents.Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3776." @default.
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- W2231516854 date "2009-05-01" @default.
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- W2231516854 title "Abstract #3776: Development of a tumor-endothelium coculture model for pharmacodynamic study of chemotherapeutic agent" @default.
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