Ho Cho Ming, Hu Fang-Wei, Lee Shiuan-Shinn, Shieh Tzong-Ming, Yu Chuan-Hang, Lin Shih-Shen, Yu Cheng-Chia
Department of Oral Maxillofacial Surgery, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan.
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
J Oral Pathol Med. 2015 Oct;44(9):693-8. doi: 10.1111/jop.12286. Epub 2014 Nov 4.
Oral squamous cell carcinoma (OSCC) is the sixth most prevalent malignancy worldwide and the third most common cancer in developing nation. Most OSCC patients relapse within months after receiving treatment. Therefore, searching the biomarkers of recurrence is urgently required to improve OSCC patient survival.
We set out to explore whether expression of ZEB1 could be triggered in oral epithelial cells (SG and FaDu) by arecoline in vitro. Control and ZEB1-knockdown arecoline-stimulated SG and FaDu were subjected to migration/invasiveness/anchorage-independent growth assay. Primary and recurrent OSCC tissues from areca quid chewers were analyzed using real-time RT-PCR analysis for ZEB1 expression.
Arecoline led to dose-dependent elevation of ZEB1 expression in SG and FaDu cells. Downregulation of ZEB1 by lentiviral infection significantly reversed arecoline-induced oncogenicity including migration ability, cell invasiveness, and anchorage-independent growth in SG and FaDu cells. Clinically, the level of ZEB1 expression was higher in recurrent OSCC tumor samples but lower in primary lesions.
Targeting ZEB1 might offer a new strategy for the treatment of OSCC patients. ZEB1 can serve as a progression and relapse marker in OSCC patients.
口腔鳞状细胞癌（OSCC）是全球第六大常见恶性肿瘤，在发展中国家是第三大常见癌症。大多数OSCC患者在接受治疗后的数月内复发。因此，迫切需要寻找复发的生物标志物以提高OSCC患者的生存率。
我们着手探究槟榔碱在体外是否能在口腔上皮细胞（SG和FaDu）中引发ZEB1的表达。对对照及ZEB1基因敲低的经槟榔碱刺激的SG和FaDu细胞进行迁移/侵袭/非锚定依赖性生长分析。对来自嚼槟榔者的原发性和复发性OSCC组织进行实时RT-PCR分析，以检测ZEB1的表达。
槟榔碱导致SG和FaDu细胞中ZEB1表达呈剂量依赖性升高。通过慢病毒感染下调ZEB1可显著逆转槟榔碱诱导的致癌性，包括SG和FaDu细胞的迁移能力、细胞侵袭能力及非锚定依赖性生长。临床上，复发性OSCC肿瘤样本中ZEB1表达水平较高，而原发性病变中较低。
靶向ZEB1可能为OSCC患者的治疗提供一种新策略。ZEB1可作为OSCC患者病情进展和复发的标志物。
