title: 15-Hydroxyprostaglandin dehydrogenase is a tumor suppressor of human gastric cancer.
abstract: Cyclooxygenase-2 (COX-2), the key enzyme in prostaglandin synthesis, is often over-expressed in human gastric cancer. Recently, 15-hydroxyprostaglandin dehydrogenase [NAD+] (15-PGDH), the key enzyme in prostaglandin degradation, was found to be down-regulated in human gastric cancer tissues, but little is known about its role in gastric tumorigenesis. In this study, expression plasmids containing 15-PGDH siRNA were constructed and transfected into the gastric cancer cell line MKN45, which expresses endogenous 15-PGDH at a high level. The 15-PGDH gene was also transfected into the gastric cancer cell line SGC7901, which expresses endogenous 15-PGDH at a low level. When compared with the empty vector transfectant, MKN45 cells stably transfected with the 15-PGDH siRNA plasmid had a significantly increased proliferation rate. In contrast, SGC7901 cells stably transfected with the 15-PGDH cDNA had a significantly decreased growth rate. Furthermore, increased expression of 15-PGDH suppressed clone formation of gastric cancer cells in plate and soft agar colony formation assays in vitro and suppressed tumor formation in athymic nude mice in vivo. Stable silencing of 15-PGDH in gastric cancer cells also enhanced cell cycle entry in vitro. These results demonstrate for the first time that 15-PGDH acts as a tumor suppressor in human gastric cancer and provide further validation for 15-PGDH as a potential therapeutic target for human gastric cancer.
authors.affiliation: State Key Laboratory of Cancer Biology & Institute of Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
authors.forename: Zhenxiong
authors.initials: Z
authors.lastname: Liu
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Lu
authors.forename: Rui
authors.initials: R
authors.lastname: Du
authors.forename: Guanhong
authors.initials: G
authors.lastname: Luo
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Huihong
authors.initials: H
authors.lastname: Zhai
authors.forename: Faming
authors.initials: F
authors.lastname: Zhang
authors.forename: Qinsheng
authors.initials: Q
authors.lastname: Wen
authors.forename: Kaichun
authors.initials: K
authors.lastname: Wu
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D034622:RNA Interference; D013274:Stomach Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D025521:Tumor Suppressor Proteins; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase