Aspirin and salicylate inhibit colon cancer medium- and VEGF-induced endothelial tube formation: correlation with suppression of cyclooxygenase-2 expression

Authors

  • M. I. Shtivelband,

    1. Division of Hematology and Vascular Biology Research Center, Institute of Molecular Medicine, University of Texas-Houston Health Science Center, Houston, TX, USA
    Search for more papers by this author
  • H. S. Juneja,

    1. Division of Hematology and Vascular Biology Research Center, Institute of Molecular Medicine, University of Texas-Houston Health Science Center, Houston, TX, USA
    Search for more papers by this author
  • S. Lee,

    1. Division of Hematology and Vascular Biology Research Center, Institute of Molecular Medicine, University of Texas-Houston Health Science Center, Houston, TX, USA
    Search for more papers by this author
  • K. K. Wu

    1. Division of Hematology and Vascular Biology Research Center, Institute of Molecular Medicine, University of Texas-Houston Health Science Center, Houston, TX, USA
    Search for more papers by this author

Kenneth K. Wu, University of Texas-Houston Health Science Center, 6431 Fannin, MSB 5.016, Houston, TX, USA.
Tel.: +1 713 500 6801; fax: +1 713 500 6812; e-mail: kenneth.k.wu@uth.tmc.edu

Abstract

Summary.  To determine whether aspirin and salicylate suppress colon cancer cell-mediated angiogenesis, we evaluated the effects of aspirin and sodium salicylate on endothelial tube formation on Matrigel. Aspirin and sodium salicylate concentration-dependently inhibited human endothelial cell (EC) tube formation induced by conditioned medium collected from DLD-1, HT-29 or HCT-116 colon cancer cells. Aspirin and sodium salicylate at pharmacological concentrations were equally effective in blocking tube formation. Neutralizing antivascular endothelial growth factor (VEGF) antibodies blocked colon cancer medium-induced tube formation. VEGF receptor 2 but not receptor 1 antibodies inhibited tube formation to a similar extent as anti-VEGF antibodies. These results indicate that VEGF interaction with VEGF receptor 2 is the primary mechanism underlying colon cancer-induced angiogenesis. Aspirin or sodium salicylate inhibited VEGF-induced tube formation in a concentration-dependent manner comparable to that of inhibition of colon cancer medium-induced endothelial tube formation. It has been shown that cyclooxygenase-2 (COX-2) is pivotal in cancer angiogenesis. We found that colon cancer medium-induced COX-2 protein expression in EC and aspirin or sodium salicylate suppressed the cancer-induced COX-2 protein levels at concentrations correlated with those that suppressed endothelial tube formation. Furthermore, aspirin and sodium salicylate inhibited COX-2 expression stimulated by VEGF. These findings indicate that aspirin and other salicylate drugs at pharmacological concentrations inhibit colon cancer-induced angiogenesis which is correlated with COX-2 suppression.

Ancillary