ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10 (ABCC10) are not primary resistance factors for cabazitaxel
10.1186/s40880-015-0003-0
- Author:
Kathawala J RISHIL
;
Wang YI-JUN
;
Shukla SUNEET
;
Zhang YUN-KAI
;
Alqahtani SAEED
;
Kaddoumi AMAL
;
Ambudkar V SURESH
;
Charles R Ashby Jr
;
Chen ZHE-SHENG
- Keywords:
ATP-binding cassette (ABC) transporters;
ATP-binding cassette subfamily B member 1 (ABCB1);
ATP-binding cassette subfamily C member 10 (ABCC10);
Taxane;
Paclitaxel;
Cabazitaxel
- From:Chinese Journal of Cancer
2015;(3):17-22
- CountryChina
- Language:Chinese
-
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.
