Differential effects of antiangiogenic compounds in neovascularization, leukocyte recruitment, VEGF production, and tumor growth in mice.
Angiogenesis and inflammation play critical roles in tumor growth. Using an in vivo tumor model, we report that thalidomide (100 mg kg(-1)day(-1)) or clotrimazole (120 mg kg(-1) day(-1)), inhibit blood vessel formation (determined by hemoglobin content), leukocyte recruitment [myeloperoxidase (MPO) activity; N-acetylglucosa-minidase (NAG) activity], and vascular endothelial growth factor production. Inhibition of angiogenesis ranged from 35% to 65%. Clotrimazole was the most potent antiangiogenic compound and the agent capable of inhibiting tumor growth. Thalidomide was able to reduce the inflammatory reaction (MPO and NAG activities) by 50% to 70%, but was unable to delay tumor development. These results suggest that for this type of solid tumor the degree of neovascularization, rather than inhibition of inflammatory cell recruitment, is a determinant factor in tumor development. As the contribution of angiogenesis and inflammation to cancer progression vary markedly among different tumor types, it may be relevant to consider these factors in cancer therapy using antiangiogenesis/antiinflammatory approaches.
Belo
Andrezza V
AV
Department of Physiology and Biophysics, Institute of Biological Sciences, Federal University of Minas, Gerais/Belo Horizonte, Brazil.
Barcelos
Lucíola S
LS
Teixeira
Mauro M
MM
Ferreira
Mônica A N D
MA
Andrade
Silvia P
SP
D000118:Acetylglucosaminidase / Q000187:drug effects; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002286:Carcinoma, Ehrlich Tumor / Q000098:blood supply / Q000188:drug therapy*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D003022:Clotrimazole / Q000494:pharmacology; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic; D009195:Peroxidase / Q000187:drug effects; D013792:Thalidomide / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000187:drug effects*
D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D042461:Vascular Endothelial Growth Factor A; D013792:Thalidomide; D009195:Peroxidase; D000118:Acetylglucosaminidase; D003022:Clotrimazole