Cyclooxygenase 2 (COX-2) is an inducible
enzyme that contributes to the generation of chronic
inflammation and the development of
cancer, and promotes neoplastic transformation, in response to chemical
carcinogens and environmental stresses. In this study, we demonstrated that a sublethal dose
photodynamic therapy (
PDT) led to inflammatory response mediated by the induction of COX-2 and release of
Prostaglandin E2 (
PGE2). Pretreatment with
N-acetylcysteine (NAC) reduced COX-2 expression and
PGE2 release induced by
PDT. The elevated COX-2 level and
PGE2 release following
PDT were inhibited by
NADPH oxidase inhibitor and NF-κB inhibitor. Inhibition of COX-2 attenuated the levels of
PGE2 and
vascular endothelial growth factor (
VEGF) following
PDT in treated
tumors, and also decreased the expression of proinflammatory mediators interleukin-1β (IL-1β) and
tumor necrosis factor-α (TNF-α). In addition,
PDT led to an appreciable accumulation of pSer15-p53/COX-2 complexes, and this association of complexes was partially inhibited by
SB203580, an inhibitor of p38. Blockage of COX-2 expression by
siRNA enhanced the transcriptional activity of p53, and facilitated
PDT-induced loss of mitochondrial membrane potential and cleavage of
caspase 3, probably due to the elevated Noxa expression disrupting the interaction of Mcl-1/Bax. Together, this study highlights the important roles of COX-2 in
PDT-induced apoptosis and
inflammation and the specific COX-2-mediated responses to
PDT initiated by
reactive oxygen species (ROS) involving the regulation of the multiple signaling pathways. These results indicate the inflammatory mediator COX-2 as a potential therapeutic target for improving
PDT efficacy.