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

Clin Exp Dermatol. 2012 Jul;37(5):527-33. doi: 10.1111/j.1365-2230.2011.04291.x. Epub 2012 Feb 2.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Disease Models, Animal
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Glucuronidase / metabolism*
  • Immunohistochemistry
  • 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

Substances

  • Biomarkers, Tumor
  • Enzyme Inhibitors
  • Photosensitizing Agents
  • Proliferating Cell Nuclear Antigen
  • heparanase
  • Glucuronidase
  • Methylene Blue