Suppr超能文献

NFκB 抑制剂诱导脑胶质瘤细胞死亡。

NFκB inhibitors induce cell death in glioblastomas.

机构信息

Centro de Estudos em Estresse Oxidativo, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

出版信息

Biochem Pharmacol. 2011 Feb 1;81(3):412-24. doi: 10.1016/j.bcp.2010.10.014. Epub 2010 Oct 30.

Abstract

Identification of novel target pathways in glioblastoma (GBM) remains critical due to poor prognosis, inefficient therapies and recurrence associated with these tumors. In this work, we evaluated the role of nuclear-factor-kappa-B (NFκB) in the growth of GBM cells, and the potential of NFκB inhibitors as antiglioma agents. NFκB pathway was found overstimulated in GBM cell lines and in tumor specimens compared to normal astrocytes and healthy brain tissues, respectively. Treatment of a panel of established GBM cell lines (U138MG, U87, U373 and C6) with pharmacological NFκB inhibitors (BAY117082, parthenolide, MG132, curcumin and arsenic trioxide) and NFκB-p65 siRNA markedly decreased the viability of GBMs as compared to inhibitors of other signaling pathways such as MAPKs (ERK, JNK and p38), PKC, EGFR and PI3K/Akt. In addition, NFκB inhibitors presented a low toxicity to normal astrocytes, indicating selectivity to cancerous cells. In GBMs, mitochondrial dysfunction (membrane depolarization, bcl-xL downregulation and cytochrome c release) and arrest in the G2/M phase were observed at the early steps of NFκB inhibitors treatment. These events preceded sub-G1 detection, apoptotic body formation and caspase-3 activation. Also, NFκB was found overstimulated in cisplatin-resistant C6 cells, and treatment of GBMs with NFκB inhibitors overcame cisplatin resistance besides potentiating the effects of the chemotherapeutics, cisplatin and doxorubicin. These findings support NFκB as a potential target to cell death induction in GBMs, and that the NFκB inhibitors may be considered for in vivo testing on animal models and possibly on GBM therapy.

摘要

由于预后不良、治疗效率低下以及与这些肿瘤相关的复发,鉴定胶质母细胞瘤(GBM)中的新靶通路仍然至关重要。在这项工作中,我们评估了核因子-κB(NFκB)在 GBM 细胞生长中的作用,以及 NFκB 抑制剂作为抗神经胶质瘤药物的潜力。与正常星形胶质细胞和健康脑组织相比,NFκB 通路在 GBM 细胞系和肿瘤标本中被发现过度刺激。用药理学 NFκB 抑制剂(BAY117082、小白菊内酯、MG132、姜黄素和三氧化二砷)和 NFκB-p65 siRNA 处理一组已建立的 GBM 细胞系(U138MG、U87、U373 和 C6),与其他信号通路抑制剂(MAPKs [ERK、JNK 和 p38]、PKC、EGFR 和 PI3K/Akt)相比,明显降低了 GBM 的活力。此外,NFκB 抑制剂对正常星形胶质细胞的毒性较低,表明对癌细胞具有选择性。在 GBM 中,在 NFκB 抑制剂治疗的早期步骤中观察到线粒体功能障碍(膜去极化、bcl-xL 下调和细胞色素 c 释放)和 G2/M 期停滞。这些事件发生在亚 G1 检测、凋亡小体形成和 caspase-3 激活之前。此外,NFκB 在顺铂耐药的 C6 细胞中被过度刺激,用 NFκB 抑制剂治疗 GBM 克服了顺铂耐药性,同时增强了化疗药物顺铂和阿霉素的作用。这些发现支持 NFκB 作为诱导 GBM 细胞死亡的潜在靶点,并且 NFκB 抑制剂可考虑在动物模型上进行体内测试,并且可能在 GBM 治疗中使用。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验