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Inhibition of Cyclooxygenase-2 Indirectly Potentiates Antitumor Effects of Photodynamic Therapy in Mice

Marcin Makowski, Tomasz Grzela, Justyna Niderla, Maciej azarczyk, Pawe Mróz, Maciej Kopeé, Magdalena Legat, Katarzyna Strusiska, Katarzyna Koziak, Dominika Nowis, Piotr Mrówka, Maria Wsik, Marek Jakóbisiak and Jakub Gob¹

Departments of Immunology [M. M., P. M., M. K., M. L., K. S., D. N., P. M., M. J., J. G.] and Histology and Embryology [T. G., J. N., M. £.] Center of Biostructure Research, and Departments of General and Vascular Surgery and Transplantation [T. G.], Internal Diseases and Hypertension [K. K.], and Laboratory Diagnostics and Clinical Immunology [M. W.], The Medical University of Warsaw, Warsaw, Poland

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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