The effect of TSPP-mediated photodynamic therapy and Parecoxib in experimental tumours

• Published in: Life sciences (1973) Vol. 117; no. 2; pp. 75 - 83
• Main Authors: Popescu, Tiberiu, Nenu, Iuliana, Aldea, Mihaela D., Olteanu, Diana, Gheban, Dan, Tatomir, Corina, Bolfa, Pompei, Muresan, Adriana, Ion, Rodica M., Filip, Adriana G.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 11-11-2014
• Subjects: Analysis of Variance; Animals; Apoptosis - drug effects; Apoptosis - radiation effects; Biomarkers - metabolism; Blotting, Western; Cancer; Carcinoma 256, Walker - drug therapy; Carcinoma 256, Walker - therapy; Cyclooxygenase 2 - metabolism; Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; In Situ Nick-End Labeling; Inflammation; Isoxazoles - therapeutic use; Male; Malondialdehyde - metabolism; Necrosis - pathology; Oxidative stress; Parecoxib; Photochemotherapy - methods; Photodynamic therapy; Porphyrins - therapeutic use; Rats; Oxidative stress; Inflammation; Parecoxib; Photodynamic therapy; Cancer
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2014.09.022

The study investigated the effects of the combined treatment Parecoxib (Pcox) and 5,10,15,20-tetra-sulphonato-phenyl-porphyrin(TSPP)-mediated photodynamic therapy on Walker 256 carcinosarcoma.
Five groups of male Wistar rats were used: the control group, treated with TSPP, group 2, irradiated 24h thereafter, group 3, treated with Pcox and irradiated 24h thereafter, groups 4 and 5 treated with combined therapies, TSPP and Pcox before irradiation, and Pcox 24h after TSPP and irradiation respectively. Tumour inflammation, growth and non-growth factors, apoptosis/necrosis rate and oxidative/nitrosative stress markers were investigated.
Malondialdehyde levels and cyclooxygenase (COX)-2 expression increased significantly in the group treated with Pcox after TSPP-PDT when compared with TSPP+IR group (p<0.05, p<0.001 respectively), in correlation with a decrease in glutathione levels (p<0.05). The quantification of apoptosis, based on the TUNEL-assay, and necrosis rate revealed an increase of apoptotic/necrotic index in the same group (p<0.05). On the other hand, Pcox administered before irradiation showed a significant increase in both vascular endothelial growth factor (VEGF) and COX-2 levels (p<0.05) and in nitric oxide production (p<0.01), when compared with the control group.
The administration of Pcox after TSPP-mediated PDT showed promising antitumoural effects, leading to an increase in oxidative and nitrosative stress as well as apoptosis/necrosis rate in tumour tissue. These results show that combined regimens that involve selective COX-2 inhibitors administration after irradiation may improve the therapeutic effectiveness of PDT.
The present study presents the effects of combined treatment, photodynamic therapy and Parecoxib, on inflammation, angiogenesis, apoptosis and oxidative stress markers in Walker carcinosarcoma. [Display omitted]