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

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

  • Chin J Cancer. 2015 Mar 5;34(3):115-20. doi: 10.1186/s40880-015-0003-0.
Rishil J Kathawala 1,  Yi-Jun Wang 2,  Suneet Shukla 3,  Yun-Kai Zhang 4,  Saeed Alqahtani 5,  Amal Kaddoumi 6,  Suresh V Ambudkar 7,  Charles R Ashby Jr 8,  Zhe-Sheng Chen 9
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. [email protected].
  • 2 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. [email protected].
  • 3 Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. [email protected].
  • 4 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. [email protected].
  • 5 Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana, Monroe, LA, 71209, USA. [email protected].
  • 6 Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana, Monroe, LA, 71209, USA. [email protected].
  • 7 Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. [email protected].
  • 8 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. [email protected].
  • 9 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, 11439, USA. [email protected].
PMID: 25962593 DOI: 10.1186/s40880-015-0003-0
Abstract

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.

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