Expression of 15-PGDH is downregulated by COX-2 in gastric cancer
Expression of 15-PGDH is downregulated by COX-2 in gastric cancer
复制标题
COX-2下调胃癌中15-PGDH的表达
DOI：
10.1093/carcin/bgm297
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发表时间：
2008-06-01
期刊：
影响因子：
4.7
通讯作者：
Fan, Daiming
中科院分区：
文献类型：
--
作者：
Liu, Zhenxiong;Wang, Xin;Fan, Daiming
为探讨环氧合酶-2(COX-2)在胃癌中的调控作用，构建了COX-2siRNA表达载体，并将其导入胃癌细胞株SGC7901。然后，应用双向电泳法和PDQuest软件分析差异表达的蛋白质。用基质辅助激光解吸电离飞行时间质谱仪分析差异蛋白质斑点。鉴定了14个在两种细胞系之间差异表达的蛋白质。15-羟基前列腺素脱氢酶(NAD(+))是前列腺素降解的关键酶，在转COX-2siRNA的SGC7901细胞中被鉴定为上调蛋白。为进一步探讨15-PGDH是否受COX-2的调控，采用免疫印迹和免疫细胞化学方法检测不同COX-2表达水平的细胞株中15-PGDH的表达。结果表明，小干扰RNA抑制COX-2的表达，上调COX-2的表达(128.57%)，增强COX-2的表达(51.72%)。在胃癌组织中，15-PGDH的表达降低，COX-2的表达增加。15-PGDH的表达与COX-2水平、肿瘤分化程度、肿瘤大小、有无淋巴结转移、TNM分期和有无淋巴结转移呈显著负相关。以上结果提示，COX-2下调15-PGDH在人胃癌中的表达，并可能与COX-2共同参与人胃癌的发生发展。
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 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. Fourteen 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 upregulated 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 upregulated (128.57%) as COX-2 was suppressed by small interfering RNA and downregulated (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, tumor, lymph node, metastasis (TNM) staging and lymph node metastasis of gastric cancer. All the results suggest that 15-PGDH is downregulated by COX-2 in human gastric cancer and may contribute to the carcinogenesis and development of human gastric cancer in combination with COX-2.