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.