Program in Individualized Medicine, Veterinary Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
Vet Comp Oncol. 2017 Jun;15(2):411-420. doi: 10.1111/vco.12177. Epub 2015 Oct 14.
ABCG2 (ATP binding cassette subfamily G, member 2) mediates resistance to a variety of cytotoxic agents. Although human ABCG2 is well characterized, the function of canine ABCG2 has not been studied previously. Feline ABCG2 has an amino acid substitution in the adenosine triphosphate-binding domain that decreases its transport capacity relative to human ABCG2. Our goal was to compare canine ABCG2-mediated chemotherapeutic drug resistance to feline ABCG2-mediated chemotherapeutic drug resistance. HEK-293 cells stably transfected with plasmid containing canine ABCG2, feline ABCG2 or no ABCG2 were exposed to carboplatin, doxorubicin, mitoxantrone, toceranib or vincristine, and cell survival was subsequently determined. Canine ABCG2 conferred a greater degree of chemotherapy resistance than feline ABCG2 for mitoxantrone. Neither canine nor feline ABCG2 conferred resistance to doxorubicin, vincristine or toceranib. Canine, but not feline, ABCG2 conferred resistance to carboplatin, a drug that is not reported to be a substrate for ABCG2 in other species.
ABCG2（ATP 结合盒亚家族 G，成员 2）介导对多种细胞毒性药物的耐药性。尽管人 ABCG2 已得到很好的描述，但犬 ABCG2 的功能以前尚未研究过。猫 ABCG2 在三磷酸腺苷结合域中有一个氨基酸取代，使其相对于人 ABCG2 的转运能力降低。我们的目标是比较犬 ABCG2 介导的化疗药物耐药性与猫 ABCG2 介导的化疗药物耐药性。用含有犬 ABCG2、猫 ABCG2 或无 ABCG2 的质粒稳定转染的 HEK-293 细胞暴露于卡铂、阿霉素、米托蒽醌、托西尼布或长春新碱，随后测定细胞存活率。犬 ABCG2 比猫 ABCG2 赋予对米托蒽醌更大程度的化疗耐药性。犬和猫 ABCG2 均未赋予阿霉素、长春新碱或托西尼布耐药性。犬 ABCG2 而非猫 ABCG2 赋予对卡铂的耐药性，卡铂是一种在其他物种中未被报道为 ABCG2 底物的药物。
