ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10 (ABCC10) are not primary resistance factors for cabazitaxel.

Autor: Kathawala RJ; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. rishil.kathawala10@my.stjohns.edu., Wang YJ; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. yijun.wang11@stjohns.edu., Shukla S; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. shuklas@mail.nih.gov., Zhang YK; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. helloyunyun@live.com., Alqahtani S; Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana, Monroe, LA, 71209, USA. alqahtsa@warhawks.ulm.edu., Kaddoumi A; Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana, Monroe, LA, 71209, USA. kaddoumi@ulm.edu., Ambudkar SV; Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. ambudkar@mail.nih.gov., Ashby CR Jr; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. ashbyc@stjohns.edu., Chen ZS; Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. chenz@stjohns.edu.
Jazyk: angličtina
Zdroj: Chinese journal of cancer [Chin J Cancer] 2015 Mar 05; Vol. 34 (3), pp. 115-20. Date of Electronic Publication: 2015 Mar 05.
DOI: 10.1186/s40880-015-0003-0
Abstrakt: Introduction: ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10 (ABCC10) proteins are efflux transporters that couple the energy derived from ATP hydrolysis to the translocation of toxic substances and chemotherapeutic drugs out of cells. Cabazitaxel is a novel taxane that differs from paclitaxel by its lower affinity for ATP-binding cassette (ABC) transporters.
Methods: We determined the effects of cabazitaxel, a novel tubulin-binding taxane, and paclitaxel on paclitaxel-resistant, ABCB1-overexpressing KB-C2 and LLC-MDR1-WT cells and paclitaxel-resistant, ABCC10-overexpressing HEK293/ABCC10 cells by calculating the degree of drug resistance and measuring ATPase activity of the ABCB1 transporter.
Results: Decreased resistance to cabazitaxel compared with paclitaxel was observed in KB-C2, LLC-MDR1-WT, and HEK293/ABCC10 cells. Moreover, cabazitaxel had low efficacy, whereas paclitaxel had high efficacy in stimulating the ATPase activity of ABCB1, indicating a direct interaction of both drugs with the transporter.
Conclusion: ABCB1 and ABCC10 are not primary resistance factors for cabazitaxel compared with paclitaxel, suggesting that cabazitaxel may have a low affinity for these efflux transporters.
Databáze: MEDLINE
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