N-acetylcysteine (NAC) inhibits cell growth by mediating the EGFR/Akt/HMG box-containing protein 1 (HBP1) signaling pathway in invasive oral cancer
N-acetylcysteine (NAC) inhibits cell growth by mediating the EGFR/Akt/HMG box-containing protein 1 (HBP1) signaling pathway in invasive oral cancer
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DOI：
10.1016/j.oraloncology.2012.08.003
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发表时间：
2013-02-01
期刊：
影响因子：
4.8
通讯作者：
Huang, Chun-Yin
中科院分区：
文献类型：
--
作者：
Lee, Ming-Fen;Chan, Chien-Yi;Huang, Chun-Yin
目的：头颈部鳞状细胞癌（SCCHN）中表皮生长因子（EGF）受体（EGFR）基因的过度表达往往与预后不良和生存不良有关。n -乙酰半胱氨酸（NAC）是一种来自蔬菜和葱属植物的化合物，具有抗肿瘤作用，但其作用机制尚不清楚。本研究的目的是探讨NAC在egfr过表达口腔癌中的作用。材料和方法：采用人舌鳞癌细胞HSC-3和SCC-4细胞株及HSC-3异种移植小鼠模型，分别在体外和体内检测NAC的抗生长作用。结果：在EGFR过表达的HSC-3口腔癌细胞中，NAC处理抑制细胞生长，同时增加转录抑制因子HMG - box-containing protein 1 （HBP1）的表达，降低EGFR/Akt的激活。HBP1敲低可减轻NAC诱导的生长停滞和细胞凋亡。最后，NAC和EGFR抑制剂AG1478共同抑制HSC-3细胞的集落形成。结论：综上所述，我们的数据表明NAC通过调节EGFR-过表达口腔癌中EGFR/Akt信号通路和HBP1表达发挥其生长抑制功能。(C) 2012 Elsevier Ltd.版权所有。
Objectives: Overexpression of the epidermal growth factor (EGF) receptor (EGFR) gene in the squamous cell carcinomas of the head and neck (SCCHN) is often associated with inauspicious prognosis and poor survival. N-acetylcysteine (NAC), a compound from some vegetables and allium species, appears anti-tumorigenesis, but the underlying mechanism is unclear. The objective of this study is to investigate the role of NAC in EGFR-overexpressing oral cancer.Materials and methods: Both HSC-3 and SCC-4 human tongue squamous carcinoma cell lines and an HSC-3 xenograft mouse model were used to test the anti-growth efficacy of NAC in vitro and in vivo, respectively.Results: NAC treatment suppressed cell growth, with concomitantly increased expression of HMG box-containing protein 1 (HBP1), a transcription suppressor, and decreased EGFR/Akt activation, in EGFR-overexpressing HSC-3 oral cancer cells. HBP1 knockdown attenuated the growth arrest and apoptosis induced by NAC. Lastly, NAC and AG1478, an EGFR inhibitor, additively suppressed colony formation in HSC-3 cells.Conclusion: Taken together, our data indicate that NAC exerts its growth-inhibitory function through modulating EGFR/Akt signaling and HBP1 expression in EGFR-overexpressing oral cancer. (C) 2012 Elsevier Ltd. All rights reserved.