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.
