Department of Nutrition and Health Sciences, Chang Jung Christian University, Tainan, Taiwan, ROC.
Oral Oncol. 2013 Feb;49(2):129-35. doi: 10.1016/j.oraloncology.2012.08.003. Epub 2012 Sep 1.
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.
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.
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.
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.
表皮生长因子受体（EGFR）基因在头颈部鳞状细胞癌（SCCHN）中的过度表达常与不良预后和生存不良相关。N-乙酰半胱氨酸（NAC）是一些蔬菜和葱属植物中的一种化合物，具有抗肿瘤作用，但具体机制尚不清楚。本研究旨在探讨 NAC 在 EGFR 过表达口腔癌中的作用。
分别使用 HSC-3 和 SCC-4 人舌鳞癌细胞系和 HSC-3 异种移植小鼠模型，在体外和体内检测 NAC 的抗生长作用。
NAC 处理抑制了 EGFR 过表达的 HSC-3 口腔癌细胞的生长，同时增加了转录抑制因子 HMG 盒蛋白 1（HBP1）的表达，并降低了 EGFR/Akt 的激活。HBP1 敲低减弱了 NAC 诱导的细胞生长停滞和凋亡。最后，NAC 和 EGFR 抑制剂 AG1478 协同抑制了 HSC-3 细胞的集落形成。
综上所述，我们的数据表明，NAC 通过调节 EGFR/Akt 信号通路和 EGFR 过表达口腔癌中的 HBP1 表达发挥其生长抑制功能。
