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This article is part of the supplement: Abstracts of the 16th International Charles Heidelberger Symposium on Cancer Research

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MDR modulation in colorectal adenocarcinoma cell lines: kinetic studies using 99mTc-sestamibi

João Casalta-Lopes1*, A Margarida Abrantes13, Joana Rio1, Mafalda Laranjo13, Bárbara Oliveiros1, A Cristina Gonçalves23, Ana B Sarmento-Ribeiro23 and M Filomena Botelho13

Author Affiliations

1 Biophysics/Biomathematics Institute (IBILI), Faculty of Medicine, University of Coimbra, Coimbra, Portugal

2 Biochemistry Institute, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

3 CIMAGO, Faculty of Medicine, University of Coimbra, Coimbra, Portugal

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BMC Proceedings 2010, 4(Suppl 2):P22  doi:10.1186/1753-6561-4-S2-P22

The electronic version of this article is the complete one and can be found online at:

Published:24 September 2010

© 2010 Casalta-Lopes et al; licensee BioMed Central Ltd.

Poster presentation

Multidrug resistance (MDR) represents one of the major setbacks to chemotherapy and can occur due to the overexpression of efflux pumps as P-glycoprotein (Pgp), multiple resistance-related protein 1 (MRP1) and lung resistance-related protein (LRP). Verapamil, a substrate for Pgp, modulates its activity. L-buthionine-sulfoximine (BSO) can be used as blocker for MRP1. In this study we aim to compare transport kinetics for sensitive and resistant human colorectal adenocarcinoma cell lines, in the presence and absence of verapamil and BSO, through 99mTc-Sestamibi.

Pgp, MRP1 and LRP expression was evaluated in resistant (LS1034) and sensitive (WiDr) human colorectal adenocarcinoma cell lines using flow-cytometry. Western blot was also used to analyze Pgp expression. Cellular transport kinetics was assessed in the presence and absence of verapamil and BSO. Retention studies were performed after cell incubation with those drugs, for different time intervals (10 and 60 minutes) and concentrations (10, 25, 50 and 100 µM), using 99mTc-Sestamibi.

Pgp expression was significantly higher (p < 0.05) in resistant cells, although LRP was also expressed. Western blotting analysis confirmed flow-cytometry results. 99mTc-Sestamibi retention percentage was significantly higher (p < 0.05) in the resistant cell line for all time-points considered. In resistant cells incubated with MDR modulators there were statistically significant differences (p < 0.05) among the modulators used but only for the first minutes after incubation with the radiotracer.

The data obtained suggest that these modulators should be used immediately before the cytotoxic drugs are administrated.