TITLE:
Efflux Pumps Modulation in Colorectal Adenocarcinoma Cell Lines: The Role of Nuclear Medicine
AUTHORS:
João Casalta-Lopes, Ana Margarida Abrantes, Mafalda Laranjo, Joana Rio, Ana Cristina Gonçalves, Bárbara Oliveiros, Ana Bela Sarmento-Ribeiro, Maria Filomena Botelho
KEYWORDS:
Multidrug Resistance, P-Glycoprotein, Multidrug Resistance-Associated Protein 1, Major Vault Protein,
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.2 No.3,
August
8,
2011
ABSTRACT: 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.