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  • Title: Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice.
    Author: Makowski M, Grzela T, Niderla J, ŁAzarczyk M, Mróz P, Kopeé M, Legat M, Strusińska K, Koziak K, Nowis D, Mrówka P, Wasik M, Jakóbisiak M, Gołab J.
    Journal: Clin Cancer Res; 2003 Nov 01; 9(14):5417-22. PubMed ID: 14614028.
    Abstract:
    PURPOSE: 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. EXPERIMENTAL DESIGN: 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.
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