贝卡替卡林（瑞贝卡霉素类似物，NSC 655649）是一种转运底物，可诱导肺癌细胞中ATP结合盒转运蛋白ABCG2的表达。
Becatecarin (rebeccamycin analog, NSC 655649) is a transport substrate and induces expression of the ATP-binding cassette transporter, ABCG2, in lung carcinoma cells.
作者信息
Robey Robert W, Obrzut Tomasz, Shukla Suneet, Polgar Orsolya, Macalou Sira, Bahr Julian C, Di Pietro Attilio, Ambudkar Suresh V, Bates Susan E
机构信息
Medical Oncology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.
出版信息
Cancer Chemother Pharmacol. 2009 Aug;64(3):575-83. doi: 10.1007/s00280-008-0908-2. Epub 2009 Jan 9.
PURPOSE
ABCG2 overexpression has been linked to resistance to topoisomerase inhibitors, leading us to examine the potential interaction between ABCG2 and becatecarin.
METHODS
Interaction with ABCG2 was determined by ATPase assay, competition of [(125)I]iodoarylazidoprazosin (IAAP) photolabeling and flow cytometry. Cellular resistance was measured in 4-day cytotoxicity assays. ABCG2 expression was measured by fluorescent-substrate transport assays and immunoblot.
RESULTS
Becatecarin competed [(125)I]-IAAP labeling of ABCG2, stimulated ATPase activity and, at concentrations greater than 10 microM, inhibited ABCG2-mediated transport. Becatecarin-selected A549 Bec150 lung carcinoma cells were 3.1-, 15-, 8-, and 6.8-fold resistant to becatecarin, mitoxantrone, SN-38 and topotecan, respectively. A549 Bec150 cells transported the ABCG2 substrates pheophorbide a, mitoxantrone and BODIPY-prazosin and displayed increased staining with the anti-ABCG2 antibody 5D3 compared to parental cells. Increased ABCG2 expression was confirmed by immunoblot.
CONCLUSIONS
Our results suggest that becatecarin is transported by ABCG2 and can induce ABCG2 expression in cancer cells.
目的
ABCG2过表达与对拓扑异构酶抑制剂的耐药性有关，这促使我们研究ABCG2与贝卡替林之间的潜在相互作用。
方法
通过ATP酶测定、[（125）I]碘芳基叠氮哌唑嗪（IAAP）光标记竞争和流式细胞术确定与ABCG2的相互作用。在4天的细胞毒性试验中测量细胞耐药性。通过荧光底物转运试验和免疫印迹法测量ABCG2表达。
结果
贝卡替林竞争ABCG2的[（125）I]-IAAP标记，刺激ATP酶活性，并且在浓度大于10 microM时，抑制ABCG2介导的转运。经贝卡替林筛选的A549 Bec150肺癌细胞对贝卡替林、米托蒽醌、SN-38和拓扑替康的耐药性分别为3.1倍、15倍、8倍和6.8倍。A549 Bec150细胞转运ABCG2底物脱镁叶绿酸a、米托蒽醌和BODIPY-哌唑嗪，与亲代细胞相比，用抗ABCG2抗体5D3染色增加。通过免疫印迹证实ABCG2表达增加。
结论
我们的结果表明，贝卡替林由ABCG2转运，并可诱导癌细胞中ABCG2的表达。
Zotero 插件