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

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DOI: 10.4236/jct.2011.23056    4,171 Downloads   8,243 Views   Citations

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 (p<0.001 and p<0.01, respectively) in the sensitive cells for all time-points considered. In resistant cells there were no significant differences when we consider the curves as a whole, considering cells incubated versus non-incubated with MDR modulators. However, for the first minutes after incubation with 99mTc-Sestamibi, there were differences among the MDR modulators used (p<0.05). Conclusions: In vitro kinetic studies using 99mTc-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.

Conflicts of Interest

The authors declare no conflicts of interest.

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J. Casalta-Lopes, A. Abrantes, M. Laranjo, J. Rio, A. Gonçalves, B. Oliveiros, A. Sarmento-Ribeiro and M. Botelho, "Efflux Pumps Modulation in Colorectal Adenocarcinoma Cell Lines: The Role of Nuclear Medicine," Journal of Cancer Therapy, Vol. 2 No. 3, 2011, pp. 408-417. doi: 10.4236/jct.2011.23056.

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