HMG-CoA reductase mediates the biological effects of retinoic acid on human neuroblastoma cells: Lovastatin specifically targets P-glycoprotein-expressing cells
HMG-CoA reductase mediates the biological effects of retinoic acid on human neuroblastoma cells: Lovastatin specifically targets P-glycoprotein-expressing cells
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DOI：
10.1038/nm0396-326
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发表时间：
1996-03-01
期刊：
影响因子：
82.9
通讯作者：
Yeger, H
中科院分区：
文献类型：
--
作者：
Dimitroulakos, J;Yeger, H
3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶，参与从头胆固醇合成和细胞周期进程，被确定为视黄酸对人神经母细胞瘤生长抑制作用的潜在介质。HMG-CoA还原酶的不可逆抑制剂，诱导广泛的，仅限于耐药的P-糖蛋白表达的神经母细胞瘤细胞系。二丁酰环腺苷酸而非视黄酸可增强这种反应。晚期转移性神经母细胞瘤患者常表现出获得性化疗耐药表型，这可能部分由P-糖蛋白介导。我们的研究支持应用或使用HMG-CoA还原酶抑制剂作为潜在的治疗药物治疗这些化疗难治性患者。
The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, involved in de novo cholesterol synthesis and cell-cycle progression, was identified as a potential mediator of the growth inhibitory effects of retinoic acid on human neuroblastoma. a nonreversible inhibitor of HMG-CoA reductase, induced extensive that was restricted to drug-resistant P-glycoprotein-expressing neuroblastoma cell lines. This response was potentiated by dibutyryl cyclic AMP but not retinoic acid. Patients with advanced-stage metastatic neuroblastoma often display an acquired chemoresistant phenotype, which may in part be mediated by P-glycoprotein. Our studies support the application or use of HMG-CoA reductase inhibitors as potential therapeutic agents in the treatment of these patients who are refractory to chemotherapy.