Its efficacy extended to a reduction in the relative tumor weight with 1.70 and 1.51-fold compared to positive control and free ETD, that manifested by a 1.72-fold reduction in both COX-2 and proliferating cell nuclear antigen mRNA (PCNA-mRNA) levels and 2.63-fold elevation in caspase-3 level in skin tumors relative to the positive control group with no hepato-and nephrotoxicity.
Because prostaglandin E<sub>2</sub> is known to promote pro-tumorigenic immune cell infiltration, increase proliferation, and inhibit keratinocyte differentiation <i>in vivo</i>, this work suggests that UVA-induced p62 acts through COX-2 to promote skin tumor growth and progression.
The positive expression rate of COX-2 in 55 skin tumors (45.5 %) was significantly higher than that in normal skin tissues (5 %) (χ (2) = 10.598 %, P < 0.05).
Since prior studies demonstrated cyclooxygenase 2 (COX-2) is necessary for DMBA/TPA tumor induction, we hypothesized that COX-2 inhibition might prevent BRAFi-accelerated skin tumors.
We conclude that (i) intrinsic epithelial COX-2 activity plays a major role in UVB-induced skin cancer, (ii) macrophage/myeloid COX-2 plays no role in UVB-induced skin cancer and (iii) either there may be another COX-2-dependent prostanoid source(s) that drives UVB skin tumor induction or there may exist a COX-2-independent pathway(s) to UVB-induced skin cancer.
Luciferase activity was non-invasively, quantitatively and repeatedly monitored in Cox-2(luc/+) mice subjected to DMBA/TPA multistage skin tumor induction.
Results from these studies support the hypothesis that combining ligand activation of PPARbeta/delta with inhibition of COX-2 activity can inhibit chemically induced skin tumor progression by modulating differentiation.
Chemoprevention of chemically induced skin tumorigenesis by ligand activation of peroxisome proliferator-activated receptor-beta/delta and inhibition of cyclooxygenase 2.
Together, these data demonstrate acute upregulation of COX-2 via UVB irradiation and suggest the need for further studies of COX-2 expression as a potential pharmacological target mediating human skin tumor development.