interleukin-8 and quininib

Colorectal cancer (CRC) is a leading cause of cancer deaths. Molecularly targeted therapies (e.g. bevacizumab) have improved survival rates but drug resistance ultimately develops and newer therapies are required. We identified quininib as a small molecule drug with anti-angiogenic activity using in vitro, ex vivo and in vivo screening models. Quininib (2-[(E)-2-(Quinolin-2-yl) vinyl] phenol), is a small molecule drug (molecular weight 283.75 g/mol), which significantly inhibited blood vessel development in zebrafish embryos (p < 0.001). In vitro, quininib reduced endothelial tubule formation (p < 0.001), cell migration was unaffected by quininib and cell survival was reduced by quininib (p < 0.001). Using ex vivo human CRC explants, quininib significantly reduced the secretions of IL-6, IL-8, VEGF, ENA-78, GRO-α, TNF, IL-1β and MCP-1 ex vivo (all values p < 0.01). Quininib is well tolerated in mice when administered at 50 mg/kg intraperitoneally every 3 days and significantly reduced tumour growth of HT-29-luc2 CRC tumour xenografts compared to vehicle control. In addition, quininib reduced the signal from a α

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents; Blood Vessels; Cell Line; Colorectal Neoplasms; Endothelial Cells; Gene Expression; HT29 Cells; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Mice, Inbred BALB C; Neovascularization, Pathologic; Phenols; Quinolines; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays; Zebrafish