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Role of multidrug resistance in photodynamic therapy
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Paper Abstract

Multidrug resistance in cancer chemotherapy is a well established phenomenon. One of the most common phenotypical changes in acquired or intrinsic multidrug resistance in human tumor cells is the overexpression of the mdrl gene product P-glycoprotein, which acts as an active efflux pump. Increased levels of P-glycoprotein are associated with resistance to a variety of anticancer drugs commonly used in tumor chemotherapy like anthracyclins, vinca- alcaloids, epipodophyllotoxins or actinomycin D. We investigated the efficacy or photodynamic therapy in the treatment of tumor cells expressing the multidrug resistance phenotype. Our data show that multidrug resistant cells are highly cross resistant to the phototoxic stain rhodamine 123 but exhibit only low degrees of cross resistance (2 - 3 -folds) to the photosensitizers Photosan-3, Clorin-2, methylene blue and meso-tetra (4- sulfonatophenyl) porphine (TPPS4). Resistance is associated with a decrease in intracellular accumulation of the photosensitizer. Verapamil, a membrane active compound known to enhance drug sensitivity in multidrug resistant cells by inhibition of P-glycoprotein, also increases phototoxicity in multidrug resistant cells. Our results imply that tumors expressing the multidrug resistance phenotype might fail to respond to photochemotherapy with rhodamine 123. On the other hand, multidrug resistance may not play an important role in photodynamic therapy with Photosan-3, Chlorin-2, methylene blue or TPPS4.

Paper Details

Date Published: 1 June 1992
PDF: 9 pages
Proc. SPIE 1645, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy, (1 June 1992); doi: 10.1117/12.60934
Show Author Affiliations
Heyke Cacile Diddens, Medizinisches Laserzentrum Luebeck GmbH (Germany)

Published in SPIE Proceedings Vol. 1645:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy
Thomas J. Dougherty, Editor(s)

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