title: The effect of TSPP-mediated photodynamic therapy and Parecoxib in  experimental tumours.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Five groups of male Wistar rats were used: the control group, treated with TSPP, group 2, irradiated 24 h thereafter, group 3, treated with Pcox and irradiated 24 h thereafter, groups 4 and 5 treated with combined therapies, TSPP and Pcox before irradiation, and Pcox 24 h after TSPP and irradiation respectively. Tumour inflammation, growth and non-growth factors, apoptosis/necrosis rate and oxidative/nitrosative stress markers were investigated.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Tiberiu
authors.initials: T
authors.lastname: Popescu
authors.forename: Iuliana
authors.initials: I
authors.lastname: Nenu
authors.forename: Mihaela D
authors.initials: MD
authors.lastname: Aldea
authors.forename: Diana
authors.initials: D
authors.lastname: Olteanu
authors.forename: Dan
authors.initials: D
authors.lastname: Gheban
authors.forename: Corina
authors.initials: C
authors.lastname: Tatomir
authors.forename: Pompei
authors.initials: P
authors.lastname: Bolfa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002279:Carcinoma 256, Walker / Q000188:drug therapy* / Q000628:therapy*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009336:Necrosis / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods*; D011166:Porphyrins / Q000627:therapeutic use*; D051381:Rats
chemical_list: D015415:Biomarkers; D007555:Isoxazoles; D011166:Porphyrins; C016136:tetraphenylporphine sulfonate; D008315:Malondialdehyde; C409945:parecoxib; D051546:Cyclooxygenase 2