Brief Article
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World J Gastroenterol. Oct 7, 2013; 19(37): 6265-6271
Published online Oct 7, 2013. doi: 10.3748/wjg.v19.i37.6265
Interaction between cyclooxygenase-2, Snail, and E-cadherin in gastric cancer cells
Xiao-Jun Liu, Zhao-Feng Chen, Hai-Long Li, Ze-Nan Hu, Min Liu, Ai-Ping Tian, Da Zhao, Jing Wu, Yong-Ning Zhou, Liang Qiao
Xiao-Jun Liu, Zhao-Feng Chen, Hai-Long Li, Ze-Nan Hu, Ai-Ping Tian, Da Zhao, Yong-Ning Zhou, Liang Qiao, The First Hospital of Lanzhou University, Lanzhou 730000, Gansu Province, China
Xiao-Jun Liu, Zhao-Feng Chen, Min Liu, Yong-Ning Zhou, Liang Qiao, Key Laboratory for Gastrointestinal Disease of Gansu Province, Lanzhou 730000, Gansu Province, China
Jing Wu, Beijing Shijitan Hospital, Beijing 100038, China
Liang Qiao, Storr Liver Unit, Westmead Millennium Institute, Western Clinical School of the Faculty of Medicine at Westmead Hospital, Westmead NSW 2145, Australia
Author contributions: Zhou YN and Qiao L designed the research; Liu XJ, Chen ZF, Li HL, Tian AP, Hu ZN and Liu M performed the laboratory studies; Wu J and Zhao D analyzed the data; Liu XJ and Chen ZF wrote the paper.
Supported by The National Natural Science Funding of China, No. 81172366; and the Fundamental Research Funds for the Central Universities, No. lzujbky-2012-224; and the Gansu Special Program for High Technology Research and Development, No. 0912TCYA027
Correspondence to: Dr. Liang Qiao, MD, PhD, Storr Liver Unit, Westmead Millennium Institute, Western Clinical School of the Faculty of Medicine at Westmead Hospital, Westmead NSW 2145, Australia. liang.qiao@sydney.edu.au
Telephone: +61-2-98459132 Fax: +61-2-98459103
Received: June 2, 2013
Revised: July 15, 2013
Accepted: August 20, 2013
Published online: October 7, 2013
Abstract

AIM: To investigate the mechanisms of how cyclooxygenase-2 (COX-2) regulates E-cadherin in gastric cancer cells.

METHODS: COX-2 expression in human gastric cancer cell lines SGC-7901, BGC-823, MGC-803 and AGS were measured at the mRNA and protein level. COX-2 rich cell line SGC-7901 was chosen for subsequent experiments. siRNA mediated gene knockdown was used to investigate the impact of COX-2 on nuclear factor-κB (NF-κB), Snail, and E-cadherin in gastric cancer cells. Gene expression was determined by Western blot and real-time polymerase chain reaction. To analyze whether NF-κB inhibition could interrupt the modulatory effect of COX-2 or prostaglandin E2 (PGE2) on E-cadherin, gastric cancer cells were treated with celecoxib or PGE2, in the presence of NF-κB specific siRNA.

RESULTS: Highest expression level of COX-2 was found in SGC-7901 cells, both at mRNA and protein levels. siRNA mediated down-regulation of COX-2 led to a reduced expression of NF-κB and Snail, but an increased expression of E-cadherin in SGC-7901 cells. siRNA mediated down-regulation of NF-κB also led to a reduced expression of E-cadherin and Snail in SGC-7901 cells. However, COX-2 expression did not alter after cells were treated with NF-κB specific siRNA in SGC-7901 cells. Treatment of SGC-7901 cells with celecoxib led to a reduced expression of Snail but an increased expression of E-cadherin. In contrast, treatment of SGC-7901 cells with PGE2 led to an increased Snail and a decreased E-cadherin. However, siRNA-mediated knockdown of NF-κB partially abolished the effect of celecoxib and PGE2 on the regulation of E-cadherin and Snail in SGC-7901 cells.

CONCLUSION: COX-2 likely functions upstream of NF-κB and regulates the expression of E-cadherin via NF-κB/Snail signaling pathway in gastric cancer cells.

Keywords: Cyclooxygenase-2, E-cadherin, celecoxib, Prostaglandin E2, Gastric cancer

Core tip: Cyclooxygenase-2 (COX-2) plays an important role in transcriptional regulation of E-cadherin in gastric cancer and other malignancies. On the contrary, prostaglandin E2 (PGE2) promotes invasion of tumor cells through down-regulating the expression of E-cadherin. Our study has provided further evidence that COX-2 functions upstream of nuclear factor-κB in the regulation of Snail and E-cadherin in gastric cancer cells. Blockade of COX-2 activity or inhibition of PGE2 production may offer some benefit in the chemoprevention and treatment of gastric cancer.