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人小细胞肺癌阿霉素耐药癌细胞系(GLC4/ADR)对灵菌红素通过激活凋亡表现出高细胞毒性敏感性。

High cytotoxic sensitivity of the human small cell lung doxorubicin-resistant carcinoma (GLC4/ADR) cell line to prodigiosin through apoptosis activation.

作者信息

Llagostera Esther, Soto-Cerrato Vanessa, Joshi Ricky, Montaner Beatriz, Gimenez-Bonafé Pepita, Pérez-Tomás Ricardo

机构信息

Department of Cellular Biology, Cancer Cell Biology Research Group, University of Barcelona, Barcelona, Spain.

出版信息

Anticancer Drugs. 2005 Apr;16(4):393-9. doi: 10.1097/00001813-200504000-00005.

Abstract

In the present study, we describe the cytotoxicity of the new drug prodigiosin (PG) in two small cell lung carcinoma (SCLC) cell lines, GLC4 and its derived doxorubicin-resistant GLC4/ADR cell line, which overexpresses multidrug-related protein 1 (MRP-1). We observed through Western blot that PG mediated cytochrome c release, caspase cascade activation and PARP cleavage, thereby leading to apoptosis in a dose-response manner. MRP-1 expression increased after PG treatment, although that does not lead to protein accumulation. The MTT assay showed no difference in sensitivity to PG between the two cell lines. Our results support PG as a potential drug for the treatment of lung cancer as it overcomes the multidrug resistance phenotype produced by MRP-1 overexpression.

摘要

在本研究中,我们描述了新型药物灵菌红素(PG)对两种小细胞肺癌(SCLC)细胞系GLC4及其衍生的阿霉素耐药GLC4/ADR细胞系的细胞毒性,后者过表达多药相关蛋白1(MRP-1)。我们通过蛋白质印迹法观察到,PG介导细胞色素c释放、半胱天冬酶级联激活和聚(ADP-核糖)聚合酶(PARP)裂解,从而以剂量反应方式导致细胞凋亡。PG处理后MRP-1表达增加,尽管这并未导致蛋白质积累。MTT试验显示这两种细胞系对PG的敏感性没有差异。我们的结果支持将PG作为治疗肺癌的潜在药物,因为它克服了由MRP-1过表达产生的多药耐药表型。

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