Apoptosis Induction and Inhibition of Colon-26 Tumour Growth and Angiogenesis: Findings On COX-1 and COX-2 Inhibitors in Vitro & in Vivo and Topical Diclofenac in Hyaluronan

Abstract

The chronic administration of non-steroidal anti-inflammatory drugs (NSAIDs) results in reduced colonic adenocarcinoma incidence¹. When administered to existing tumours, NSAIDs induce tumour regression². Other states susceptible to NSAIDs include basal cell carcinoma (BCC) and the precancerous lesion actinic keratosis (AK)³ using a topical delivery system, HYAL CT1101 (3% diclofenac in 2.5% hyaluronan). The advent of inducible cyclooxygenase (COX-2) raises the question as to its role in tumour growth and development. The role of COX of any isoform remains speculative. Tumour derived prostaglandin-E₂ (PGE₂) may result in inhibition of macrophage and NK cell function or there may be direct effects on tumour cells. COX-2 has been reported in many human colonic adenocarcinomas but not all^{4, 5}. Studies with the dual COX-1/2 inhibitor sulindac have shown that familial intestinal polyposis is reduced in the clinic⁶, whilst the murine equivalent is modified by selective COX-2 inhibition or gene deletion⁷.