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Introduction:ATP-binding cassette subfamily B member 1(ABCB1) and subfamily C member 10(ABCCIO) 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 paclitaxelresistant,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.
Introduction: ATP-binding cassette subfamily B member 1 (ABCB1) and subfamily C member 10 (ABCCIO) 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 that 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, but paclitaxel had high efficacy in stimulating the ATPase activity of ABCB1, indicating a direct interaction of Both drugs with the transporter. Confocal: 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.