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.
复制标题
DOI：
10.1186/s40880-015-0003-0
复制
发表时间：
2015-03-05
影响因子：
--
通讯作者：
Chen ZS
中科院分区：
文献类型：
--
作者：
Kathawala RJ;Wang YJ;Shukla S;Zhang YK;Alqahtani S;Kaddoumi A;Ambudkar SV;Ashby CR Jr;Chen ZS
ATP结合盒亚家族B成员1（ABCB 1）和亚家族C成员10（ABCC 10）蛋白是外排转运蛋白，它们将ATP水解产生的能量与有毒物质和化疗药物转运出细胞偶联。卡巴他赛是一种新型紫杉烷，与紫杉醇的不同之处在于其对ATP结合盒（ABC）转运蛋白的亲和力较低。我们通过计算耐药程度和测量ABCB 1转运蛋白的ATP酶活性，确定卡巴他赛（一种新型微管蛋白结合紫杉烷）和紫杉醇对紫杉醇耐药、ABCB 1过表达的KB-C2和LLC-MDR 1-WT细胞以及紫杉醇耐药、ABCC 10过表达的HEK 293/ABCC 10细胞的影响。与紫杉醇相比，在KB-C2、LLC-MDR 1-WT和HEK 293/ABCC 10细胞中观察到卡巴他赛耐药性降低。此外，卡巴他赛的疗效较低，而紫杉醇在刺激ABCB 1的ATP酶活性方面疗效较高，表明两种药物与转运蛋白直接相互作用。与紫杉醇相比，ABCB 1和ABCC 10不是卡巴他赛的主要耐药因素，表明卡巴他赛可能对这些外排转运蛋白具有低亲和力。
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.