title: Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice.
abstract: OBJECTIVE
  The aim of the present study was to potentiate the antitumor effectiveness of photodynamic therapy (PDT). A cDNA microarray analysis was used to evaluate the gene expression pattern after Photofrin-mediated PDT to find more effective combination treatment with PDT and inhibitor(s) of the identified gene product(s) overexpressed in tumor cells.
  
  
  METHODS
  Atlas Mouse Stress Array was used to compare the expression profile of control and PDT-treated C-26 cells. The microarray results have been confirmed using Western blotting. Cytostatic/cytotoxic in vitro assay as well as in vivo tumor models were used to investigate the antitumor effectiveness of PDT in combination with cyclooxygenase (COX) 2 inhibitors.
  
  
  RESULTS
  PDT induced the expression of 5 of 140 stress-related genes. One of these genes encodes for COX-2, an enzyme important in the tumor progression. Inhibition of COX-2 in vitro with NS-398, rofecoxib, or nimesulide, or before PDT with nimesulide did not influence the therapeutic efficacy of the treatment. Administration of a selective COX-2 inhibitor after PDT produced potentiated antitumor effects leading to complete responses in the majority of treated animals.
  
  
  CONCLUSIONS
  COX-2 inhibitors do not sensitize tumor cells to PDT-mediated killing. However, these drugs can be used to potentiate the antitumor effectiveness of this treatment regimen when administered after tumor illumination.
authors: Departments of Immunology, The Medical University of Warsaw, Warsaw, Poland.
authors: Marcin
authors: M
authors: Makowski
authors: Tomasz
authors: T
authors: Grzela
authors: Justyna
authors: J
authors: Niderla
authors: Maciej
authors: M
authors: ŁAzarczyk
authors: Paweł
authors: P
authors: Mróz
authors: Maciej
authors: M
authors: Kopeé
authors: Magdalena
authors: M
authors: Legat
authors: Katarzyna
authors: K
authors: Strusińska
authors: Katarzyna
authors: K
authors: Koziak
authors: Dominika
authors: D
authors: Nowis
authors: Piotr
authors: P
authors: Mrówka
authors: Maria
authors: M
authors: Wasik
authors: Marek
authors: M
authors: Jakóbisiak
authors: Jakub
authors: J
authors: Gołab
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D017323:Dihematoporphyrin Ether / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008027:Light; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D010778:Photochemotherapy; D011451:Prostaglandin-Endoperoxide Synthases; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D017323:Dihematoporphyrin Ether; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases