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Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms
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SYSNO ASEP 0473195 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Glycol porphyrin derivatives and temoporfin elicit resistance to photodynamic therapy by different mechanisms Tvůrce(i) Králová, Jarmila (UMG-J) RID
Kolář, Michal (UMG-J) RID, ORCID
Kahle, Michal (UMG-J)
Truksa, Jaroslav (BTO-N) RID, ORCID
Lettlová, Sandra (BTO-N)
Balusiková, K. (CZ)
Bartůněk, Petr (UMG-J) RIDČíslo článku 44497 Zdroj.dok. Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 7, Mar 15 (2017)Poč.str. 15 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova Glycol porphyrin derivates ; chemotherapy ; cancer ; multidrug resistance Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Biochemistry and molecular biology Vědní obor RIV – spolupráce Biotechnologický ústav - Genetika a molekulární biologie CEP LO1220 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Institucionální podpora UMG-J - RVO:68378050 ; BTO-N - RVO:86652036 UT WOS 000396339500001 DOI https://doi.org/10.1038/srep44497 Anotace The development of drug resistance is a major problem which often occurs during anticancer chemotherapies. Photodynamic therapy (PDT) has been studied as an alternative treatment modality for drug-resistant tumors, however the question of resistance to PDT and potential cross-resistance with chemotherapy has yet to be fully answered. To investigate the mechanism of resistance to PDT, we developed an in vitro experimental model system in a mouse mammary carcinoma cell line 4T1. We used two ethylene glycol derivatives of tetraphenylporphyrin, and tetraphenylchlorin derivative, temoporfin, as photosensitizers (PS). PDT-resistant clones were obtained by exposure to a set concentration of PS followed by irradiation with increasing light doses. PDT resistance to soluble glycol porphyrins was mediated mainly by increased drug efflux through ABCB1 (P-glycoprotein) as we demonstrated by specific ABCB1 knockdown experiments, which in turn rescued the sensitivity of resistant cells to PDT. In contrast, resistance raised to temoporfin, which is generally more lipophilic than glycol porphyrins, elicited mechanism based on sequestration of the drug to lysosomes. The resistance that is acquired from a particular PS could be overcome by using a different PS, which is not susceptible to the same mechanism(s) of resistance. Elucidation of the underlying mechanisms in various types of resistance might facilitate improvements in PDT treatment design. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2017
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