Salicylate inhibition of rat mammary carcinogenesis and angiogenesis in female rat compatible with misoprostol administration.
Epidemiological data suggest that non-steroidal anti-inflammatory drugs prevent colon cancer. The evidence for other types of tumour is less conclusive, though animal and in vitro studies indicate that they may be effective against mammary cancer cells. We assessed the effect of dietary acetylsalicylic and salicylic acid against dimethylbenzanthracene-induced rat tumours. Tumour angiogenesis was also investigated to explore the mechanism responsible for salicylate effect. Mammary tumours were induced in female Sprague-Dawley rats fed with different amounts of acetylsalicylic and salicylic acid. Serum vascular endothelial growth factor concentrations were measured and vascularization of basement membrane proteins injected in vivo (Matrigel) was determined by evaluation of haemoglobin content to assess the extent to which angiogenesis was inhibited. Dimethylbenzanthracene-induced carcinogenesis was inhibited by both acids and there was a log-dose/response correlation between the tumour diameter and salicylate concentration. Salicylic acid seems more effective than acetylsalicylic acid. Vascular endothelial growth factor was less concentrated in treated animals than in the controls and so was Matrigel haemoglobin. The mechanism involved, however, is still uncertain, though concomitant inhibition of tumour angiogenesis may be an important component. The documented salicylate serum VEGF modulation is interesting also for presence of the flk-1 receptor in mammary tumour cells of our model. Although misoprostol is a prostaglandin analogous its concomitant administration did not compromise the salicylate anti-tumour effect.
Ghezzo
Franco
F
Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, I-10043 Orbassano (TO), Italy. franco.ghezzo@unito.it
Cesano
Luigi
L
Mognetti
Barbara
B
Pesce
Eugenio
E
Pirro
Elisa
E
Corvetti
Giovanna
G
Berta
Giovanni N
GN
Zingaro
Barbara
B
Di Carlo
Francesco
F
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000098:blood supply / Q000503:physiopathology*; D016595:Misoprostol / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D010120:Oxytocics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020156:Salicylic Acid / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D010120:Oxytocics; D016595:Misoprostol; D020156:Salicylic Acid; D001241:Aspirin