Knockdown of EGFR inhibits growth and invasion of gastric cancer cells.
The epidermal growth factor receptor (EGFR) is an oncogenic trans-membranous receptor, which is overexpressed in multiple human cancers. However, the role of EGFR in gastric cancer (GC) is still elusive. In this study, we aimed to investigate the expression and molecular mechanisms of EGFR in GC cells. Forty cases of GC and the corresponding adjacent non-cancerous tissues (ANCT) were collected, and the expression of EGFR was assessed using immunohistochemistry in biopsy samples. Furthermore, EGFR signaling was blocked by constructed recombinant small hairpin RNA lentiviral vector (Lv-shRAGE) used to transfect into human GC SGC-7901 cells. The expression of AKT, proliferating cell nuclear antigen (PCNA) and matrix metallopeptidase-9 (MMP-9) was detected by real-time PCR and western blotting assays. Cell proliferative activities and invasive capability were, respectively, determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and Transwell assays. Cell apoptosis and cycle distribution were analyzed by flow cytometry. EGFR was found highly expressed in cancer tissues compared with the ANCT and correlated with lymph node metastases. Knockdown of EGFR reduced cell proliferation and invasion of GC with decreased expression of AKT, PCNA and MMP-9 and induced cell apoptosis and cycle arrest. Upregulation of EGFR expression is associated with lymph node metastases of GC, and blockade of EGFR signaling suppresses growth and invasion of GC cells through AKT pathway, suggesting that EGFR may represent a potential therapeutic target for this aggressive malignancy.
Department of Gastroenterological Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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Y
Zhen
Department of Gastroenterological Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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Guanghui
Department of Gastroenterological Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
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Z
Xiefu
D015153:Blotting, Western; D049109:Cell Proliferation / Q000502:physiology*; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D016086:Lentivirus; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013274:Stomach Neoplasms / Q000378:metabolism*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured
D018809:Proliferating Cell Nuclear Antigen; D034741:RNA, Small Interfering; D013778:Tetrazolium Salts; D013844:Thiazoles; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D020780:Matrix Metalloproteinase 9; C022616:thiazolyl blue