Peng TL, Chen J, Mao W, Liu X, Tao Y, Chen LZ, Chen MH. Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer. World J Gastroenterol 2009; 15(14): 1719-1729 [PMID: 19360915 DOI: 10.3748/wjg.15.1719]
Corresponding Author of This Article
Min-Hu Chen, MD, PhD, Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, Guangdong Province, China. chenminhu@vip.163.com
Article-Type of This Article
Original Articles
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Tie-Li Peng, Jie Chen, Wei Mao, Xin Liu, Min-Hu Chen, Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Yu Tao, Department of Pathology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Lian-Zhou Chen, Digestive system tumor tissue bank, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, Guangdong Province, China
Author contributions: Peng TL and Chen J contributed equally to this work; Peng TL and Chen J performed the research and wrote the paper; Mao W organized the figures and patients’ data; Liu X, Tao Y and Chen LZ performed immunohistochemical staining assays; Chen MH designed the research and supervised the writing and organization process.
Correspondence to: Min-Hu Chen, MD, PhD, Department of Gastroenterology, The First Affiliated Hospital of Sun Yat-Sen University, 58 Zhongshan II Road, Guangzhou 510080, Guangdong Province, China. chenminhu@vip.163.com
Telephone: +86-20-87332916
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Received: December 2, 2008 Revised: February 18, 2009 Accepted: February 25, 2009 Published online: April 14, 2009
Abstract
AIM: To determine the functional significance of aryl hydrocarbon receptor (AhR) in gastric carcinogenesis, and to explore the possible role of AhR in gastric cancer (GC) treatment.
METHODS: RT-PCR, real-time PCR, and Western blotting were performed to detect AhR expression in 39 GC tissues and five GC cell lines. AhR protein was detected by immunohistochemistry (IHC) in 190 samples: 30 chronic superficial gastritis (CSG), 30 chronic atrophic gastritis (CAG), 30 intestinal metaplasia (IM), 30 atypical hyperplasia (AH), and 70 GC. The AhR agonist tetrachlorodibenzo-para-dioxin (TCDD) was used to treat AGS cells. MTT assay and flow cytometric analysis were performed to measure the viability, cell cycle and apoptosis of AGS cells.
RESULTS: AhR expression was significantly increased in GC tissues and GC cell lines. IHC results indicated that the levels of AhR expression gradually increased, with the lowest levels in CSG, followed by CAG, IM, AH and GC. AhR expression and nuclear translocation were significantly higher in GC than in precancerous tissues. TCDD inhibited proliferation of AGS cells via induction of growth arrest at the G1-S phase.
CONCLUSION: AhR plays an important role in gastric carcinogenesis. AhR may be a potential therapeutic target for GC treatment.