磺脲类格列苯脲抑制人肺癌细胞多药耐药蛋白(MRP1)活性。
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帕恩L，德鲁金L，库尔图瓦A，特里查特Y，吉乌佐A，法德尔O
磺脲类格列苯脲抑制人肺癌细胞多药耐药蛋白(MRP1)活性。
中国药理学杂志，2001 2月;132(3):778-84。
- PubMed ID
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11159731 (在PubMed］
- 摘要
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1.格列苯脲是一种广泛用于治疗非胰岛素依赖型糖尿病的磺脲类药物，已被证明可以抑制各种atp结合盒(ABC)转运体的活性。在本研究中，研究了它对多药耐药蛋白1 (MRP1)的影响，MRP1是一种ABC外排泵，具有多药耐药和处理有机阴离子的作用。2.在MRP1过表达的肺癌GLC4/Sb30细胞中，格列苯脲通过抑制MRP1相关的钙黄素外排，以剂量依赖性的方式强烈增加了钙黄素(MRP1的阴离子染料底物)的细胞内积累。相比之下，格列苯脲不改变亲代对照GLC4细胞中的钙黄素水平。另一种磺脲类，甲苯丁酰胺，对GLC4/Sb30和GLC4细胞中钙黄素的积累没有影响。3.此外，发现在12.5微米下使用格列本脲能强烈增强GLC4/Sb30细胞对长春新碱(一种由MRP1处理的抗癌药物)的敏感性。4. Efflux of carboxy-2',7'-dichlorofluorescein, an anionic dye handled by the ABC transporter MRP2 sharing numerous substrates with MRP1 and expressed at high levels in liver, was also strongly inhibited by glibenclamide in isolated rat hepatocytes. 5. In summary, glibenclamide reversed MRP1-mediated drug resistance likely through inhibiting MRP1 activity and blocked organic anion efflux from MRP2-expressing hepatocytes. Such effects associated with the known inhibitory properties of glibenclamide towards various others ABC proteins suggest that this sulphonylurea is a general inhibitor of ABC transporters.