Carcinogenesis Advance Access published online on January 3, 2008
Carcinogenesis, doi:10.1093/carcin/bgm297
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Expression of 15-PGDH is down-regulated by COX-2 in gastric cancer
1 State key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China
2 Corresponding author Kaichun Wu M.D./Ph.D. State key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, 15 Changle Western Rd., Xi'an, Shaanxi Province, 710032, P.R.China. Phone: 86-29-84775221; Fax: 86-29-82539041; E-mail: kaicwu{at}fmmu.edu.cn
To explore the proteins regulated by cyclooxygenase-2 (COX-2) in gastric cancer, the expression plasmid of COX-2siRNA was constructed and transfected into gastric cancer cell line SGC7901. Then, two-dimensional electrophoresis (2-DE) and the PDQuest software analysis were applied to discover the differentially expressed proteins. The differential protein spots were analyzed by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). 14 differentially expressed proteins between the two cell lines were identified. 15-hydroxyprostaglandin dehydrogenase [NAD+] (15-PGDH), a key enzyme in prostaglandin degradation, was identified as an up-regulated protein in SGC7901 cells transfected with the COX-2siRNA plasmid. To further explore whether the 15-PGDH is regulated by COX-2, Western blotting and immunocytochemical assay were performed to detect the expression of 15-PGDH in different cell lines with different expression level of COX-2. The results showed that the expression of 15-PGDH was up-regulated (128.57%) as COX-2 was suppressed by siRNA, and down-regulated (51.72%) as COX-2 was enhanced by COX-2 cDNA transfection in gastric cancer cells. In tissue specimens with gastric cancer, there was a decreased expression of 15-PGDH and an increased expression of COX-2 simultaneously. A significantly negative correlation of 15-PGDH expression was found to COX-2 level, tumor differentiation, TNM staging and lymph node metastasis of gastric cancer. All the results suggest that 15-PGDH is down-regulated by COX-2 in human gastric cancer and may contribute to the carcinogenesis and development of human gastric cancer in combination with COX-2.
Key Words: 15-PGDH • COX-2 • Prostaglandin • 2-DE • Gastric cancer • Proteome analysis
* The first two authors contributed equally to this work
Received September 15, 2007; revised December 16, 2007; accepted December 17, 2007.
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