15-hydroxyprostaglandin dehydrogenase is a tumor suppressor of human gastric cancer
15-hydroxyprostaglandin dehydrogenase is a tumor suppressor of human gastric cancer
复制标题
15-羟基前列腺素脱氢酶是人类胃癌的肿瘤抑制因子
DOI：
10.4161/cbt.10.8.12896
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发表时间：
2010-10-15
影响因子：
3.6
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Liu, Zhenxiong;Wang, Xin;Fan, Daiming
环氧合酶-2（考克斯-2）是前列腺素合成的关键酶，在胃癌组织中表达异常。近年来，研究发现前列腺素降解的关键酶15-羟前列腺素脱氢酶（15-PGDH）在胃癌组织中表达下调，但其在胃癌发生中的作用尚不清楚。本研究构建了含15-PGDH siRNA的表达质粒，并转染高表达内源性15-PGDH的胃癌细胞系MKN 45。将15-PGDH基因转染胃癌细胞系SGC 7901，其以低水平表达内源性15-PGDH。与空载体转染相比，稳定转染15-PGDH siRNA质粒的MKN 45细胞的增殖率显著增加。相反，稳定转染15-PGDH cDNA的SGC 7901细胞生长速率显著降低。此外，15-PGDH的表达增加抑制体外平板和软琼脂集落形成试验中胃癌细胞的克隆形成，并抑制体内无胸腺裸鼠的肿瘤形成。胃癌细胞中15-PGDH的稳定沉默也增强了体外细胞周期进入。这些结果首次证明了15-PGDH在人胃癌中作为肿瘤抑制因子，并进一步验证了15-PGDH作为人胃癌的潜在治疗靶点。
Cyclooxygenase-2 (COX-2), the key enzyme in prostaglandin synthesis, is often overexpressed in human gastric cancer. Recently, 15-hydroxyprostaglandin dehydrogenase [NAD(+)] (15-PGDH), the key enzyme in prostaglandin degradation, was found to be downregulated 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.