Zebrafish have proved to be invaluable for modeling complex physiological processes shared by all vertebrate animals. Resistance of cancers and other diseases to drug treatment can occur owing to expression of the ATP-dependent multidrug transporters ABCB1, ABCG2, and ABCC1, either because of expression of these transporters by the target cells to reduce intracellular concentrations of cytotoxic drugs at barrier sites such as the blood-brain barrier (BBB) to limit penetration of drugs into privileged compartments, or by affecting the absorption, distribution, and excretion of drugs administered orally, through the skin, or directly into the bloodstream. We describe the drug specificity, cellular localization, and function of zebrafish orthologs of multidrug resistance ABC transporters with the goal of developing zebrafish models to explore the physiological and pathophysiological functions of these transporters. Finally, we provide context demonstrating the utility of zebrafish in studying cancer drug resistance. Our ultimate goal is to improve treatment of cancer and other diseases which are affected by ABC multidrug resistance transporters.

事实证明，斑马鱼对于模拟所有脊椎动物共有的复杂生理过程具有无价的价值。癌症和其他疾病对药物治疗的耐药性可能是由于 ATP 依赖性多药物转运蛋白 ABCB1、 ABCG2和 ABCC1 的表达而发生的，或者是因为靶细胞表达这些转运蛋白以降低细胞毒性药物在屏障位点的细胞内浓度，例如作为血脑屏障（BBB），限制药物渗透到特权区室，或通过影响口服、通过皮肤或直接进入血流的药物的吸收、分布和排泄。我们描述了多药耐药ABC 转运蛋白斑马鱼直系同源物的药物特异性、细胞定位和功能，目的是开发斑马鱼模型来探索这些转运蛋白的生理和病理生理功能。最后，我们提供了证明斑马鱼在研究癌症耐药性方面的实用性的背景。我们的最终目标是改善癌症和其他受 ABC 多药耐药转运蛋白影响的疾病的治疗。