The inhibition of colon-26 adenocarcinoma development and angiogenesis by topical diclofenac in 2.5% hyaluronan

• Published in: Cancer research (Chicago, Ill.) Ill.), 1997-05, Vol.57 (9), p.1625-1629
• Main Authors: SEED, M. P, BROWN, J. R, FREEMANTLE, C. N, PAPWORTH, J. L, COLVILLE-NASH, P. R, WILLIS, D, SOMERVILLE, K. W, ASCULAI, S, WILLOUGHBY, D. A
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - drug therapy; Administration, Topical; Animals; Antineoplastic agents; Apoptosis - drug effects; Biological and medical sciences; Cell Survival - drug effects; Chemotherapy; Colonic Neoplasms - drug therapy; Cyclooxygenase Inhibitors - administration & dosage; Diclofenac - administration & dosage; Hyaluronic Acid - administration & dosage; Medical sciences; Mice; Mice, Inbred BALB C; Mitosis - drug effects; Neovascularization, Pathologic - prevention & control; Pharmaceutical Vehicles; Pharmacology. Drug treatments; Platelet Endothelial Cell Adhesion Molecule-1 - analysis
• ISSN: 0008-5472; 1538-7445

Topical diclofenac in 2.5% hyaluronan inhibits basal cell carcinoma, actinic keratosis, and murine colon-26 growth in vivo. colon-26 tumor growth was preceded by angiogenesis and reduced apoptotic and mitotic indices. Diclofenac reduced proliferation and viability in vitro, and stimulated apoptosis. Hyaluronan inhibited proliferation and viability at 1 mg/ml but was inactive below this level. Topical application of diclofenac inhibited tumor prostaglandin synthesis and retarded angiogenesis and tumor growth (ratio of treatment:control, 0.174). The mitotic index remained unaltered in vivo, whereas the apoptotic index and necrosis were increased. Topical vehicle exhibited slight antitumor and antiangiogenesis activity. The substantial quantities of diclofenac delivered locally in hyaluronan may exhibit antitumor activity in similar fashion to those seen in vitro and explain its clinical efficacy.