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Role of ABC Transporters in the Chemoresistance of Human Gliomas
Abstract
Malignant gliomas are frequently chemoresistant and this resistance seems to depend on at least two mechanisms. First, the poor penetration of many anticancer drugs across the blood-brain barrier (BBB), the blood-cerebrospinal fluid barrier (BCSFB) and blood-tumor barrier (BTB), due to their interaction with several ATP-binding cassette (ABC) drug efflux transporters that are overexpressed by the endothelial or epithelial cells of these barriers. Second, resistance may involve the tumor cells themselves. Although ABC drug efflux transporters in tumor cells confer multidrug resistance (MDR) on several other solid tumors, their role in gliomas is unclear. This review focuses on astrocytes and summarizes the current state of knowledge about the expression, distribution and function of ABC transporters in normal and tumor astroglial cells. The recognition of anticancer drugs by ABC transporters in astroglial cells and their participation in the multidrug resistance phenotype of human gliomas is discussed.
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Increased production of NO elicited by statins reduces activity of Pgp/ABCB1 and BCRP/ABCG2 in hCMEC/D3 cells.
“the increased production of NO elicited by the statins reduced the activity of at least two proteins -Pgp/ABCB1 and BCRP/ABCG2 -that are involved in the apical extrusion of drugs in hCMEC/D3 cells (Tai et al., 2009) and in vivo (Declèves et al., 2006;Mercer et al., 2009;Robey et al., 2010).”
From The association of statins plus LDL receptor‐targeted liposome‐encapsulated doxorubicin increases in vitro drug delivery across blood–brain barrier cells (2012) · cites this paper as Declèves et al., 2006
Doxorubicin is a substrate of Pgp/ABCB1, MRP1/ABCC1 and BCRP/ABCG2.
“Doxorubicin, for instance, is a very effective anticancer drug against glioblastoma cells in vitro, but since it is a substrate of Pgp/ABCB1, MRP1/ABCC1 and BCRP/ABCG2, its delivery across the BBB is hampered and it is ineffective clinically at treating this tumour.”
From The association of statins plus LDL receptor‐targeted liposome‐encapsulated doxorubicin increases in vitro drug delivery across blood–brain barrier cells (2012) · cites this paper as Declèves et al., 2006
The brain microvascular endothelium has high levels of drug efflux pumps of the ABC transporter family.
“In addition, having no fenestrations and many tight junctions, the brain microvascular endothelium has high levels of drug efflux pumps of the ABC transporter family (Declèves et al., 2006;Mercer et al., 2009;Robey et al., 2010).”
From The association of statins plus LDL receptor‐targeted liposome‐encapsulated doxorubicin increases in vitro drug delivery across blood–brain barrier cells (2012) · cites this paper as Declèves et al., 2006
Both tumour cells and BBB endothelial cells are rich in ATP-binding cassette (ABC) transporters, like P-glycoprotein (Pgp/ABCB1), multidrug resistance-related proteins (MRPs/ABCCs) and breast cancer resistance protein (BCRP/ABCG2) that extrude drugs from the luminal side of endothelial cells back into the blood and out of the tumour cells.
“Both tumour cells and BBB endothelial cells are rich in ATP-binding cassette (ABC) transporters, like P-glycoprotein (Pgp/ABCB1), multidrug resistance-related proteins (MRPs/ABCCs) and breast cancer resistance protein (BCRP/ABCG2) that extrude drugs from the luminal side of endothelial cells back into the blood and out of the tumour cells (Declèves et al., 2006;Mercer et al., 2009;Robey et al., 2”
From The association of statins plus LDL receptor‐targeted liposome‐encapsulated doxorubicin increases in vitro drug delivery across blood–brain barrier cells (2012) · cites this paper as Declèves et al., 2006
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The Blood-Brain Barrier in Brain Homeostasis and Neurological Diseases
Weiss, N., Miller, F., Cazaubon, S., & Couraud, P.-O. (2009) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2008.10.022 · Cited by 731
Phase I Study of GRN1005 in Recurrent Malignant Glioma
Drappatz, J., Brenner, A., Wong, E. T., Eichler, A., Schiff, D., Groves, M. D., Mikkelsen, T., Rosenfeld, S., Sarantopoulos, J., Meyers, C. A., et al. (2013) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-12-2481 · Cited by 190
Pinzón‐Daza, M., Garzón, R., Couraud, P., Romero, I., Weksler, B., Ghigo, D., Bosia, A., & Riganti, C. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.02103.x · Cited by 84
Metadata
- Authors
- Decleves, X., Amiel, A., Delattre, J.-Y., & Scherrmann, J.-M.
- Venue
- Current Cancer Drug Targets
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2006-08-01
- Volume
- 6
- Issue
- 5
- Pages
- 433-445
- ISSN
- 1568-0096
- Cited by
- 65
- References
- 0
- Language
- en
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