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

Cancer Communications

Charles R Ashby¹  Zhe-Sheng Chen¹  Suneet Shukla²  Amal Kaddoumi²  Rishil J Kathawala²  Saeed Alqahtani³  Yi-Jun Wang⁴  Yun-Kai Zhang⁴  Suresh V Ambudkar⁴ 

[1] Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of Louisiana, Monroe, USA;Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John’Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, USA;s University, Queens, USA

关键词: ATP-binding cassette (ABC) transporters;    ATP-binding cassette subfamily B member 1 (ABCB1);    ATP-binding cassette subfamily C member 10 (ABCC10);    Taxane;    Paclitaxel;    Cabazitaxel;   

DOI  :  10.1186/s40880-015-0003-0

学科分类：肿瘤学

来源: Springer

【 摘 要 】

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. 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. 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. 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.

【 授权许可】

CC BY