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Efflux Pumps Modulation in Colorectal Adenocarcinoma Cell Lines: The Role of Nuclear Medicine

Journal of Cancer Therapy 2011年第3期2卷 408-417页

作者： Joao Casalta-Lopes Ana Margarida Abrantes Mafalda Laranjo Joana Rio Ana Cristina Goncalves Barbara Oliveiros Ana Bela Sarmento-Ribeiro Maria Filomena Botelho Biophysics Unit IBILIFaculty of MedicineUniversity of CoimbraCoimbraPortugal Centre of Investigation on Cancer Envi-ronmentGenetics and OncobiologyFaculty of MedicineUniversity of CoimbraCoimbraPortugal Institute of Nuclear Sciences Applied to Health University of CoimbraCoimbraPortugal Applied Molecular Biology Unit Faculty of MedicineUniversity of CoimbraCoimbraPortugal.

Introduction: Multidrug resistance (MDR) is one of the major problems of chemotherapy. Overexpression of efflux pumps, such as P-glycoprotein (Pgp), multiple resistance-related protein 1 (MRP-1) and lung resistance protein (LRP) can lead to MDR. Verapamil and L-buthionine-sulfoximine (BSO) are two modulators of these proteins. This study aims to compare 99mTc-Sestamibi transport kinetics in human colorectal adenocarcinoma cell lines, in the presence and absence of the MDR modulators verapamil and BSO. Material and Methods: MDR proteins expression was evaluated in sensitive (WiDr) and resistant (LS1034) human colorectal adenocarcinoma cell lines. Intracellular and plasma membrane Pgp and MRP1, and LRP expression was analyzed by flow-cytometry and western blot. Cellular transport kinetics was assessed using 99mTc-Sestamibi. MDR modulation was evaluated though retention studies in resistant cells after incubation with the modulators. Results: Pgp expression was significantly higher (p≤0.001) in resistant cells. These results were confirmed by western blot analysis. 99mTc-Sestamibi uptake and retention percentage were significantly higher (p99mTc-Sestamibi, there were differences among the MDR modulators used (p99mTc-Sestamibi could indicate MDR phenotype in colorectal adenocarcinoma cells. As the modulators used showed a reversion of the retention profile only for the first minutes, their administration should occur immediately before the administration of cytotoxic drugs.

关键词： Multidrug Resistance P-Glycoprotein Multidrug Resistance-Associated protein 1 major vault protein

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