The inhibition of colon-26 adenocarcinoma development and angiogenesis by topical diclofenac in 2.5% hyaluronan.
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.
Seed
M P
MP
Department of Experimental Pathology, Saint Bartholomew's Hospital and the Royal London School of Medicine and Dentistry, United Kingdom. m.p.seed@mds.qmw.ac.uk
Brown
J R
JR
Freemantle
C N
CN
Papworth
J L
JL
Colville-Nash
P R
PR
Willis
D
D
Somerville
K W
KW
Asculai
S
S
Willoughby
D A
DA
D000230:Adenocarcinoma / Q000188:drug therapy*; D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004008:Diclofenac / Q000008:administration & dosage*; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis / Q000187:drug effects; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D014677:Pharmaceutical Vehicles; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis
D016861:Cyclooxygenase Inhibitors; D014677:Pharmaceutical Vehicles; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D004008:Diclofenac; D006820:Hyaluronic Acid