A76

OBJECTIVES: Angiogenesis is the base for solid tumor growth and dissemination, recently anti-angiogenic drugs have begun to show promise in clinical trials. In addition to angiogenesis, it has become increasingly clear that inflammation is a key component in tumor insurgence.
 >We propose to identify molecules and pathways involved in cancer progression in order to prevent neoplastic development and metastatic dissemination, targeting the tumor stroma and inflammatory infiltrate component associated to angiogenesis. The potential beneficial effects of the synthetic triterpenoid methyl 2-cyano-3,12-dioxoolean-1,9-dien-28-oate (CDDO-Me) was evaluated on in vitro and invivo angiogenic assays.
 >MATERIALS: Human Umbilical Vein Endothelial Cells (HUVECs) and human Kaposi’s Sarcoma Immortalized cells (KS-Imm) were grown in complete M199 and DMEM medium, respectively.
 >6 weeks male C57BL/6N mice were purchased from Charles River Laboratories (Italy).
 >CDDO-Me was kindly provided by Michael Sporn, Department of Pharmacology, Dartmouth Medical School, Hanover (USA).
 >RESULTS: We assessed the activity of this novel compound that has shown a potent antiangiogenic activity at really low dosages. In vivo it inhibited angiogenesis in the Matrigel sponge assay and KS-Imm tumor growth. In vitro it was able to prevent endothelial cells tubulogenesis when cultured on Matrigel.
 >In HUVE cells this compound doesn’t seem to interfere with Akt pathway but it can inhibit the activation of erk1/2 pathway after stimulation with VEGF. These data can partially explain its potent anti-angiogenic activity but further studies are necessary to full understand their promising property.
 >CONCLUSIONS: Inflammation, angiogenesis and the microenvironment are increasingly recognized as an angiogenic stimulus in cancer. The repression of the NF-kB pathway suggests anti-inflammatory effects for the anti-oxidant compounds that may also have an indirect role in angiogenesis inhibition. Many of the molecules studies inhibit inflammation-associated angiogenesis by targeting cells in the tumor microenvironment

Sixth AACR International Conference on Frontiers in Cancer Prevention Research-- Dec 5-8, 2007; Philadelphia, PA