Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Nov 7, 2011; 17(41): 4572-4580
Published online Nov 7, 2011. doi: 10.3748/wjg.v17.i41.4572
Effects of cyclooxygenase-2 on human esophageal squamous cell carcinoma
Li Zhang, Yong-Dong Wu, Peng Li, Jun Tu, Ying-Lin Niu, Cai-Min Xu, Shu-Tian Zhang
Li Zhang, Yong-Dong Wu, Peng Li, Ying-Lin Niu, Shu-Tian Zhang, Department of Gastroenterology, Beijing Friendship Hospital Affiliated with the Capital Medical University, Beijing 100050, China
Jun Tu, Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, United States
Cai-Min Xu, Department of Biochemistry and Molecular Biology, National Laboratory of Medical Molecular Biology, Institute of Basic Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China
Author contributions: Zhang ST designed the research; Wu YD, Li P and Tu J performed the research; Niu YL and Xu CM analyzed the data; Zhang L wrote the paper.
Supported by The National Natural Science Foundation of China, No. 81071974; The National 863 High Technology Research and Development Plan of China, No. 2007AA02Z4Z4
Correspondence to: Shu-Tian Zhang, PhD, MD, Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, 95 Yong’an Road, Beijing 100050, China. niuziyue1@hotmail.com
Telephone: +86-10-63014411 Fax: +86-10-63020006
Received: April 19, 2011
Revised: June 16, 2011
Accepted: June 23, 2011
Published online: November 7, 2011
Abstract

AIM: To study the relationship between the cyclooxygenase (COX)-2 gene and the proliferation and apoptosis of esophageal squamous carcinoma EC109 cells.

METHODS: The techniques of RNA interference (RNAi) and cell transfection, as well as the levels of oncogenicity in nude mice, were used to study the role of COX-2 in the esophageal squamous carcinoma cell (ESCC) line EC109. Following RNAi and transfection, Western blotting analysis was used to determine the expression of the COX-2 protein. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction assay was used to evaluate cell growth, and flow cytometry was used to detect cell apoptosis.

RESULTS: Western blotting analysis demonstrated that COX-2 expression was significantly reduced in EC109 cells treated with COX-2-specific short interfering RNA (siRNA) but was increased in EC109 cells transfected with COX-2. Furthermore, COX-2 siRNA treatment inhibited cell proliferation (P < 0.01) and induced apoptosis in EC109 cells, as determined by an MTT assay and by flow cytometry, respectively. In contrast, transfected COX-2 led to increased cell proliferation (P < 0.05) and decreased apoptosis in EC109 cells. In addition, combination treatment of cells with COX-2 siRNA and aspirin had a synergistic effect (P < 0.01). For experiments measuring tumorigenicity, xenograft tumors of a greater volume and weight were found in the COX-2 group compared with other groups (P < 0.05). A large dose of aspirin inhibited tumor growth in nude mice effectively (P < 0.05), and the rate of tumor suppression was 51.8% in the high-dose aspirin group.

CONCLUSION: COX-2 plays a very critical role in ESCC carcinogenesis, and COX-2 siRNA combined with aspirin has the potential to be an anticancer therapy for the treatment of ESCC.

Keywords: Esophageal squamous cell carcinoma; Cyclooxygenase-2; Aspirin; Cell proliferation; Apoptosis; Synergismt; Transfection; RNA interference