Combination of cetuximab with met inhibitor in control of cetuximab-resistant oral squamous cell carcinoma

American Journal of Translational Research

Hua Yang¹  Wenxing Li²  Leyna G Liu³  Chuzi Mo⁴  Yang Xun⁵ 

[1] Department of Basic Medicine and Biomedical Engineering, School of Stomatology and Medicine, Foshan University, Foshan 528000, Guangdong, China;Department of Medicine, Division of Rheumatology, Milton S. Hershey Medical Center at Penn State University, Hershey, PA 17033, USA;Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming 650204, Yunnan, China;Portola High School, 1001 Cadence, Irvine, CA 92618, U.S.A;The Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, Yunnan, China

关键词: Oral squamous cell carcinoma;    cetuximab resistance;    HGF;    Met;    Akt;    ERK1/2;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

Objective: To investigate the underlying molecular mechanisms contributing to oral squamous cell carcinoma (OSCC) cell resistance to the epidermal growth factor receptor (EGFR) inhibitor. Materials and methods: OSCC cell lines HSC-2 and HSC-3 were assessed in vitro for drug treatment, cell viability, and gene expression and the online gene expression in OSCC tissues was analyzed for association with OSCC prognosis. Results: HSC-2 and HSC-3 cells expressed high EGFR levels, but hepatocyte growth factor (HGF) treatment induced cetuximab resistance, whereas the Met inhibitor PHA-665752 as well as Met siRNA was able to restore OSCC cell sensitivity to cetuximab. HGF treatment induced tumor cells to express p-Akt and p-ERK1/2. In contrast, the activity of Akt and ERK1/2 was suppressed by treatment with PHA-665752, Met siRNA, or their combination. Furthermore, Met was highly expressed in OSCC tissues and associated with a poor patient survival, while Met/HGF-activated Akt also was associated with a poor patient survival. Conclusions: This study demonstrates that Met/HGF expression results in OSCC resistance to cetuximab and tumor recurrence after cetuximab therapy; thus, inhibition of Met/HGF activity could restore OSCC sensitivity to cetuximab.

【 授权许可】

CC BY-NC