Methylene blue photodynamic therapy in malignant melanoma decreases expression of proliferating cell nuclear antigen and heparanases

• Published in: Clinical and experimental dermatology Vol. 37; no. 5; pp. 527 - 533
• Main Authors: Wagner, M., Suarez, E. R., Theodoro, T. R., Machado Filho, C. D. A. S., Gama, M. F. M., Tardivo, J. P., Paschoal, F. M., Pinhal, M. A. S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.07.2012; Wiley-Blackwell; Oxford University Press
• Subjects: Animals; Biological and medical sciences; Biomarkers, Tumor - metabolism; Dermatology; Disease Models, Animal; Enzyme Inhibitors - therapeutic use; Female; Glucuronidase - metabolism; Immunohistochemistry; Medical sciences; Melanoma, Experimental - drug therapy; Melanoma, Experimental - metabolism; Melanoma, Experimental - pathology; Methylene Blue - therapeutic use; Mice; Mice, Nude; Photochemotherapy - methods; Photosensitizing Agents - therapeutic use; Proliferating Cell Nuclear Antigen - metabolism; Skin Neoplasms - drug therapy; Skin Neoplasms - metabolism; Skin Neoplasms - pathology; Tumors of the skin and soft tissue. Premalignant lesions; Antigen; Photodynamic therapy; Treatment; Dermatology; Malignant melanoma; Malignant tumor; Cancer
• ISSN: 0307-6938; 1365-2230
• DOI: 10.1111/j.1365-2230.2011.04291.x

Summary Background.  Malignant melanoma (MM) is a very aggressive tumour. Although surgical excision of MM in the early stages has a very good prognosis, it often fails to completely inhibit tumour progression. Methylene blue photodynamic therapy (MB‐PDT) is a technique that induces tissue damage by reactive oxygen species (ROS). Aim.  To investigate the efficacy of and potential use of MB‐PDT in restraining the aggressiveness of MM by analysing levels of proliferating cell nuclear antigen (PCNA) and heparanase (HPSE, a molecular marker of cell invasion) in a mouse model. Methods.  Expression of PCNA and two HPSE isoforms were analysed using immunohistochemistry (IHC) after MB‐PDT in mice. Tumour volume and weight were also measured. Results.  Two treatments with MB‐PDT promoted a decrease of 99% decrease in tumour volume and 75% in tumour weight compared with untreated mice (P < 0.05). Using IHC, a decrease in expression of 75% for PCNA and 95% for both HPSE isoforms (P < 0.05) was found. Conclusion.  MB‐PDT is a cheap and efficient method of decreasing MM volume and thus disease progression. This reduction is mediated by downregulation of PCNA and heparanases.