Photodynamic therapy (
PDT) is a method for treating pre-cancerous and cancerous lesions of the skin, bladder and oral cavity. However, tumour recurrence after
PDT remains problematic despite good initial response. Some studies have shown that
PDT induces
vascular endothelial growth factor (
VEGF) expression in human
oral squamous cell carcinoma and other organs. However, little is known about
VEGF expression applied to
PDT in human
carcinoma cell lines. No studies have been conducted of
PDT using
Npe6 (Npe6-mediated PDT), a second-generation
photosensitizer, in the human oral
carcinoma cell line, HSC-3 cells. We investigated the expression of
VEGF, c-jun and c-fos proto-oncogenes in HSC-3 cells in response to Npe6-mediated
PDT. We also addressed the possibility that oxidative damage induced by
PDT could lead to an angiogenic response, via
VEGF expression. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that Npe6-mediated
PDT induced the expression of mRNAs for
VEGF, c-jun and c-fos in time- and concentration-dependent manners.
Desferrioxamine (DFX), an
iron chelator, induced
VEGF expression, but the expression pattern was different to that of Npe6-mediated
PDT. The expression mRNAs for
VEGF, c-jun and c-fos induced by Npe6-mediated
PDT were inhibited by
SB203580,
p38 MAPK inhibitors, and the expression of
VEGF mRNA was inhibited by
cycloheximide (
CHX), a protein synthesis inhibitor. The c-jun
mRNA expression was inhibited, whereas the c-fos
mRNA expression was enhanced by
N-acetyl-L-cysteine (NAC), a
free radical scavenger. We conclude that Npe6-mediated
PDT induces the expression of
VEGF, c-jun and c-fos in human oral
carcinoma cell line, HSC-3 cell, and at least partly, through the activation of
p38 MAPK.