摘要
ABC转运蛋白家族在癌症耐药性中具有重要作用,包含7个亚家族(ABCA、ABCB、ABCC、AB-CD、ABCE、ABCF和ABCG),每个亚家族各具不同的结构和功能.这些转运蛋白通过移除细胞内的化疗药物或其他有害物质,降低药效,从而导致多药耐药(MDR)现象.其中,ABCB1(P-gp)和ABCG2(BCRP)是被研究最多的成员,其过表达与多种癌症的耐药性密切相关.研究显示,ABCB家族能有效排除如紫杉醇、阿霉素和长春新碱等抗癌药物,而ABCC家族也与多药耐药有显著相关性.ABCD家族在多种癌症中也展现出潜在的耐药机制.尽管已有多种抑制剂针对这些转运蛋白以恢复化疗效用,但临床应用仍面临挑战.深入理解ABC转运蛋白在癌症发展中的复杂角色,将为未来设计新型抗癌策略提供重要思路.对全家族成员的功能特征及相互作用的系统研究,将有助于找到有效的治疗方法以克服癌症耐药性.
Abstract
The ABC transporter family plays a crucial role in cancer drug resistance,comprising seven sub-families(ABCA,ABCB,ABCC,ABCD,ABCE,ABCF,and ABCG),each with distinct structural and functional character-istics.These transporters reduce the efficacy of chemotherapy drugs by removing them or other harmful substances from cells,leading to multidrug resistance(MDR).Among them,ABCB1(P-gp)and ABCG2(BCRP)are the most studied,with their overexpression closely linked to resistance in various cancers.Research indicates that the ABCB family effec-tively expels anticancer drugs like paclitaxel,doxorubicin,and vincristine,while the ABCC family is also significantly as-sociated with MDR.The ABCD family shows potential resistance mechanisms in several cancer types.Although various inhibitors have been developed to target these transporters and restore chemotherapy effectiveness,clinical application re-mains challenging.A deeper understanding of the complex roles of ABC transporters in cancer progression will provide valuable insights for designing novel anticancer strategies.Systematic studies of the functional characteristics and interac-tions of all family members will aid in finding effective treatments to overcome cancer drug resistance.
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