Li Qing, Shu Yan
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, Baltimore, Maryland USA ; Institute of Clinical Pharmacology, Central South University, Changsha, Hunan 410078 China.
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland at Baltimore, Baltimore, Maryland USA.
Mol Cell Ther. 2014 May 27;2:15. doi: 10.1186/2052-8426-2-15. eCollection 2014.
Membrane transporters play critical roles in moving a variety of anticancer drugs across cancer cell membrane, thereby determining chemotherapy efficacy and/or toxicity. The retention of anticancer drugs in cancer cells is the result of net function of efflux and influx transporters. The ATP-binding cassette (ABC) transporters are mainly the efflux transporters expressing at cancer cells, conferring the chemo-resistance in various malignant tumors, which has been well documented over the past decades. However, the function of influx transporters, in particular the solute carriers (SLC) in cancer cells, has only been recently well recognized to have significant impact on cancer therapy. The SLC transporters not only directly bring anticancer agents into cancer cells but also serve as the uptake mediators of essential nutrients for tumor growth and survival. In this review, we concentrate on the interaction of SLC transporters with anticancer drugs and nutrients, and their impact on chemo-sensitivity or -resistance of cancer cells. The differential expression patterns of SLC transporters between normal and tumor tissues may be well utilized to achieve specific delivery of chemotherapeutic agents.
膜转运蛋白在多种抗癌药物跨癌细胞膜转运过程中发挥着关键作用,从而决定化疗效果和/或毒性。抗癌药物在癌细胞内的蓄积是外排转运蛋白和内流转运蛋白综合作用的结果。ATP结合盒(ABC)转运蛋白主要是癌细胞上表达的外排转运蛋白,在多种恶性肿瘤中赋予化疗耐药性,在过去几十年中已有充分记载。然而,内流转运蛋白,特别是癌细胞中的溶质载体(SLC)的功能,直到最近才被充分认识到对癌症治疗有重大影响。SLC转运蛋白不仅直接将抗癌药物带入癌细胞,还作为肿瘤生长和存活所需营养物质的摄取介质。在这篇综述中,我们专注于SLC转运蛋白与抗癌药物和营养物质的相互作用,以及它们对癌细胞化疗敏感性或耐药性的影响。正常组织和肿瘤组织之间SLC转运蛋白的差异表达模式可被充分利用以实现化疗药物的特异性递送。