How to Cite
Abstract
Introduction. Non-steroidal anti-inflammatory drugs and, in particular, diclofenac, are considered as drugs with a potentially anticarcinogenic effect and can be used to enhance the effects of antitumor therapy.
Aim. To evaluate the effectiveness of diclofenac as a potential modifier of photodynamic therapy (PDT) in vivo in Ehrlich tumor model in mice.
Materials and methods. The study was conducted on male mice of BALB/C strain with intradermally grafted Ehrlich carcinoma. Experimental procedures were performed on day 7 after tumor inoculation. The control group did not receive treatment, in one group only diclofenac was administered, photosensitizer was administered in three groups (photoditazin, 5 mg / kg, intravenously once), tumor was irradiated with a laser (ALOD, 662 nm) or PDT was performed, respectively, and in three groups the procedures indicated above in each case were combined with the administration of diclofenac. 2 series of experiments were conducted to assess the reproducibility of the results. The size of the tumor was recorded after exposure.
Results. In the first series of the experiment, in all groups with the administration of diclofenac (45 mg/kg/day), a high animal mortality was unexpectedly observed, associated with the toxic effect of diclofenac, which required a change in its administration regime and dose (15 mg/kg) in the second series of the experiment. The administration of diclofenac did not significantly affect the efficacy of PDT, and also did not have a modifying effect in other groups (with the introduction of a photosensitizer or laser irradiation) compared with similar groups without diclofenac. PDT with photoditazine turned out to be the most effective treatment regimen: in 8 out of 10 mice in the group from the 21th day after procedure the tumors were not recorded, the animals were alive until the end of the observation for 60 days. The introduction of a photosensitizer and radiation without a photosensitizer did not lead to a significant inhibition of tumor growth.
Conclusion. In vivo on a model of intradermally grafted Ehrlich tumor in mice, diclofenac does not have a modifying effect on the antitumor effects of PDT.
References
Agostinis P, Berg K, Cengel KA, et al. Photodynamic therapy of cancer: an overview. CA Cancer J Clin. 2011;61:250-281. DOI: 10.3322/caac.20114
Bahner JD, Bordeaux JS. Non-melanoma skin cancers: photodynamic therapy, cryotherapy, 5-fluorouracil, imiquimod, diclofenac, or what? Facts and controversies. Clin Dermatol 2013;31:792-798. DOI: 10.1016/j.clindermatol.2013.08.020
Wan MT, Lin JY Current evidence and applications of photodynamic therapy in dermatology. Clin Cosmet Investig Dermatol. 2014;7:145-163. DOI: 10.2147/CCID.s35334
Buytaert E, Dewaele M, Agostinis P Molecular effectors of multiple cell death pathways initiated by photodynamic therapy. Biochem. Biophys. Acta. 2007;1776:86-107. DOI: 10.1016/j.bbcan.2007.07.001
Hasan T. Using cellular mechanisms to develop effective combinations of photodynamic therapy and targeted therapies. J Natl Compr Canc Netw. 2012;10(Suppl 2):23-26.
Henderson BW, Donovan JM. Release of prostaglandin E2 from cells by photodynamic treatment in vitro. Cancer Res. 1989;49:6896-6900.
Penning LC, Keirse MJ, Van Steveninck J, Dubbelman TM. Ca(2+)-mediated prostaglandin E2 induction reduces haematoporphyrin-derivative-induced cytotoxicity of T24 human bladder transitional carcinoma cells in vitro. Biochem J. 1993;292(Pt 1):237-240.
Hendrickx N, Volanti C, Moens U, et al. Up-regulation of cyclooxygenase-2 and apoptosis resistance by p38 MAPK in hypericin-mediated photodynamic therapy of human cancer cells. J Biol Chem. 2003;278:52231-52239. DOI: 10.1074/jbc.M307591200
Makowski M, Grzela T, Niderla J, et al. Inhibition of cyclooxygenase-2 indirectly potentiates antitumor effects of photodynamic therapy in mice. Clin Cancer Res. 2003;9:5417-5422.
Pantziarka P, Sukhatme V, Bouche G, et al. Repurposing Drugs in Oncology (ReDO)-diclofenac as an anti-cancer agent. Ecancermedicalscience. 2016;10:610-616. DOI: 10.3332/ecancer.2016.610
Hendrickx N, Volanti C, Moens U, et al. Up-regulation of cyclooxygenase-2 and apoptosis resistance by p38 MAPK in hypericin-mediated photodynamic therapy of human cancer cells. J Biol Chem. 2003;278:52231-52239. DOI: 10.1074/jbc.M307591200
Falkowski M, Skogstad S, Shahzidi S, et al. The effect of cyclooxygenase inhibitor diclofenac on experimental murine colon carcinoma. Anticancer Res. 2003;23:2303-2308.
Wallace J. Humane Endpoints and Cancer Research ILAR Journal, Volume 41, Issue 2, 2000, Pages 87-93.
Стуков А.Н., Иванова М.А., Никитин А.К., и др. Индекс роста опухоли как интегральный критерий эффективности противоопухолевой терапии в эксперименте. // Вопросы онкологии. - 2001. - Т.47, №5. - С. 616618. [Stukov AN, Ivanova MA, Nikitin AK, et al. Tumor growth index as an integral criterion for the efficacy of antineoplastic therapy under experimental conditions. Voprosy onkologii. 2001;47(5):616-618. (In Russ).].
Ferrario A, Von Tiehl K, Wong S, et al. Cyclooxygenase-2 inhibitor treatment enhances photodynamic therapy-mediated tumor response. Cancer Res. 2002;62:3956-3961.
Hendrickx N, Dewaele M, Buytaert E, et al. Targeted inhibition of p38alpha MAPK suppresses tumor-associated endothelial cell migration in response to hypericin-based photodynamic therapy. Biochem Biophys Res Commun. 2005;337:928-935. DOI: 10.1016/j.bbrc.2005.09.135
Committee for veterinary medicinal products. Diclofenac. Summary report [Internet]. [updated 2003 Sep; cited 2018 Sep 18]. Available from: http://www.ema.europa. eu/docs/en_GB/document_library/Maximum_Residue_ Limits_-_Report/2009/11/WC500013751.pdf.
Valle BL, D’Souza T, Becker KG, et al. Non-steroidal anti-inflammatory drugs decrease E2F1 expression and inhibit cell growth in ovarian cancer cells. PLoS one. 2013;24:e61836. DOI: 10.1371/journal.pone.0061836
Gottfried E, Lang SA, Renner K, et al. New aspects of an old drug-diclofenac targets MYC and glucose metabolism in tumor cells. PLoS One. 2013;9:e66987. DOI: 10.1371/journal.pone.0066987
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
© АННМО «Вопросы онкологии», Copyright (c) 2019