Ibuprofen and hydrogel-released ibuprofen in the reduction of inflammation-induced migration in melanoma cells

• Published in: British journal of dermatology (1951) Vol. 161; no. 1; pp. 25 - 33
• Main Authors: Redpath, M., Marques, C.M.G., Dibden, C., Waddon, A., Lalla, R., MacNeil, S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2009; Wiley-Blackwell
• Subjects: Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Apoptosis - drug effects; Biological and medical sciences; Cell Movement - drug effects; Delayed-Action Preparations - pharmacology; Dermatology; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology; ibuprofen; Ibuprofen - pharmacology; inflammation; Inflammation - drug therapy; Medical sciences; Melanoma - pathology; melanoma migration; nonsteroidal anti-inflammatory drugs; Skin Neoplasms - pathology; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - pharmacology; Tumors of the skin and soft tissue. Premalignant lesions; tumour necrosis factor-α; Non steroidal antiinflammatory agent; tumour necrosis factor-α; Dermatology; Ibuprofen; Malignant melanoma; Inflammation; Malignant tumor; Hydrogel; Tumor necrosis factor α; Cancer; melanoma migration, nonsteroidal anti-inflammatory drugs
• ISSN: 0007-0963; 1365-2133
• DOI: 10.1111/j.1365-2133.2009.09220.x

Summary Background  There is growing evidence that inflammation may exacerbate cancer metastasis and several clinical studies show that taking nonsteroidal anti‐inflammatory drugs appears to reduce metastases. Objectives  The aims of this study were: (i) to examine the effects of ibuprofen on the major proinflammatory cytokine tumour necrosis factor (TNF)‐α induction of migration of C8161 and HBL human melanoma cells; (ii) to develop ibuprofen‐releasing hydrogels (Pluronics F127) for future topical use in reducing metastatic spread of primary melanoma; and (iii) to examine whether the actions of ibuprofen might be explained by induction of apoptosis. Methods  Melanoma cells were exposed to 300 U mL−1 TNF‐α for a 24‐h period prior to making a scratch wound to which ibuprofen or ibuprofen‐loaded hydrogels were then added. The effects of relevant concentrations of ibuprofen on cell viability and apoptosis were examined. Results  Ibuprofen at 10−3 mol L−1 significantly reduced TNF‐α‐stimulated migration of both cell types to that of nonstimulated cells (P < 0·001). TNF‐α‐unstimulated cell migration was not significantly affected. Cells responded similarly to SS and SR forms of ibuprofen. Cells treated with ibuprofen sodium salt‐loaded hydrogels showed a significant reduction in migration when compared with unloaded hydrogels. Ibuprofen induced apoptosis in HBL cells but had no effect on C8161 melanoma cells apoptosis at concentrations that reduced migration. Conclusions  These results demonstrate that TNF‐α upregulated malignant melanoma migration in vitro and that this could be reduced by ibuprofen both in solution and delivered from a hydrogel. These effects of ibuprofen cannot be attributed simply to induction of apoptosis.