Polgar Orsolya, Robey Robert W, Bates Susan E
National Cancer Institute, Medical Oncology Branch, Center for Cancer Research, NIH, 9000 Rockville Pike, Building 10, Room 13N240, Bethesda, MD 20892, USA.
Expert Opin Drug Metab Toxicol. 2008 Jan;4(1):1-15. doi: 10.1517/17425255.4.1.1.
ABCG2 was discovered in multi-drug-resistant cancer cells, with the identification of chemotherapeutic agents, such as mitoxantrone, flavopiridol, methotrexate and irinotecan as substrates. Later, drugs from other therapeutic groups were also described as substrates, including antibiotics, antivirals, HMG-CoA reductase inhibitors and flavonoids. An expanding list of compounds inhibiting ABCG2 has also been generated. The wide variety of drugs transported by ABCG2 and its normal tissue distribution with highest levels in the placenta, intestine and liver, suggest a role in protection against xenobiotics. ABCG2 also has an important role in the pharmacokinetics of its substrates. Single nucleotide polymorphisms of the gene were shown to alter either plasma concentrations of substrate drugs or levels of resistance against chemotherapeutic agents in cell lines. ABCG2 was also described as the determinant of the side population of stem cells. All these aspects of the transporter warrant further research aimed at understanding ABCG2's structure, function and regulation of expression.
ABCG2是在多药耐药癌细胞中发现的，已确定米托蒽醌、黄酮哌啶醇、甲氨蝶呤和伊立替康等化疗药物为其底物。后来，其他治疗组的药物也被描述为底物，包括抗生素、抗病毒药物、HMG-CoA还原酶抑制剂和黄酮类化合物。抑制ABCG2的化合物清单也在不断增加。ABCG2转运的药物种类繁多，且在胎盘、肠道和肝脏中正常组织分布水平最高，这表明它在抵御外源性物质方面发挥着作用。ABCG2在其底物的药代动力学中也起着重要作用。该基因的单核苷酸多态性被证明会改变底物药物的血浆浓度或细胞系中对化疗药物的耐药水平。ABCG2也被描述为干细胞侧群的决定因素。转运蛋白的所有这些方面都值得进一步研究，以了解ABCG2的结构、功能和表达调控。
