mTHPC-mediated photodynamic treatment up-regulates the cytokines VEGF and IL-1alpha

Photochem Photobiol. 2012 Mar-Apr;88(2):432-9. doi: 10.1111/j.1751-1097.2011.01062.x. Epub 2012 Jan 10.

Abstract

Photodynamic therapy (PDT) of cancer induces oxidative stress, which intervenes in the expression of cytokines by tumor cells. The cytokines might have either a positive or a negative impact on tumor eradication. Here, we studied the expression of cytokines vascular endothelial growth factor (VEGF) and interleukin-1alpha (IL-1alpha) in the human epidermoid carcinoma A-431 cells following m-tetra(3-hydroxyphenyl)-chlorin (mTHPC)-mediated PDT in vitro and assessed the IL-1alpha effect on VEGF expression. Quantitative polymerase chain reaction and enzyme-linked immunosorbent assay revealed the enhanced production of VEGF and IL-1alpha both on mRNA and protein levels by mTHPC-loaded cells after light exposure. The silencing of IL1A by small interfering RNA resulted in decreased production of IL-1alpha and a reduced amount of VEGF. Furthermore, exogenous recombinant IL-1alpha stimulated the VEGF expression after PDT. Thus, in addition to the cytotoxic action on the A-431 cells, mTHPC-mediated PDT stimulated the production of VEGF and IL-1alpha, and IL-1alpha contributed to the VEGF overexpression. These data establish IL-1alpha as a possible target of combined cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / metabolism
  • Cell Line, Tumor
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Gene Silencing
  • Humans
  • Interleukin-1alpha / antagonists & inhibitors
  • Interleukin-1alpha / genetics
  • Interleukin-1alpha / metabolism*
  • Light
  • Mesoporphyrins / pharmacology*
  • Photochemotherapy*
  • Photosensitizing Agents / pharmacology*
  • Polymerase Chain Reaction
  • RNA, Small Interfering / genetics
  • Signal Transduction / drug effects
  • Signal Transduction / radiation effects
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Interleukin-1alpha
  • Mesoporphyrins
  • Photosensitizing Agents
  • RNA, Small Interfering
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • temoporfin