| 环氧合酶-2基因沉默对食管鳞癌花生四烯酸代谢通路的影响 |
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| 引用本文： | 庄则豪,王凤霞,魏晶晶,孙静文,邹方明,杨立勇. 环氧合酶-2基因沉默对食管鳞癌花生四烯酸代谢通路的影响[J]. 中国肿瘤临床, 2012, 39(23): 1873-1876. DOI: 10.3969/j.issn.1000-8179.2012.23.002 |
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| 作者姓名： | 庄则豪 王凤霞 魏晶晶 孙静文 邹方明 杨立勇 |
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| 作者单位： | ①.福建医科大学附属第一医院消化内科（福州市350004） |
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| 摘 要： | 目的 探讨siRNA沉默环氧合酶-2（COX-2）对食管鳞癌（ESCC）细胞增殖的影响，观察花生四烯酸（AA）代谢酶COX-2和5-脂氧合酶（5-LOX）、其下游产物PGE2和LTB4及细胞凋亡相关基因表达的变化，寻找低浓度COX-2酶抑制剂引起AA代谢转向5-LOX途径并促进ESCC细胞增殖的解决方案。 方法 设空白对照、脂质体对照、随机序列siRNA和COX-2 siRNA组，筛选高效COX-2 siRNA序列作用于ESCC细胞株TE-1及Eca109，四唑单钠法检测细胞增殖、RT-PCR和Western blot检测mRNA及蛋白、ELISA法检测PGE2和LTB4，流式细胞技术检测细胞周期。 结果 与空白对照组相比，COX-2 siRNA转染后，TE-1及Eca109细胞出现增殖抑制（抑制率分别为45.86%和48.99%，均P < 0.05）；COX-2 mRNA、蛋白表达及PGE2下降（P < 0.05），5-LOX表达及LTB4无明显变化（P>0.05）；G1期细胞比例分别为63.16 %和68.15 %（空白对照组分别为58.93%和33.02%，P < 0.05）；Bcl-2 mRNA及蛋白表达下降而Caspase-9、Bax表达上调（P < 0.05）。 结论 高效COX-2抑制可以避免COX-2低水平抑制引起的AA向5-LOX途径代谢分流，从而有效实现ESCC细胞增殖抑制。
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| 关 键 词： | RNAi干扰 环氧合酶-2 5-脂氧合酶 食管鳞癌 细胞凋亡 |
| 收稿时间： | 2012-03-26 |
Effects of Cyclooxygenase-2 Gene Silencing on the Arachidonic Acid Metabolism Pathway of Esophageal Squamous Cell Carcinoma Cells |
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| Zehao ZHUANG,Fengxia WANG,Jingjing WEI,Jingwen SUN,Fangming ZOU,Liyong YANG. Effects of Cyclooxygenase-2 Gene Silencing on the Arachidonic Acid Metabolism Pathway of Esophageal Squamous Cell Carcinoma Cells[J]. Chinese Journal of Clinical Oncology, 2012, 39(23): 1873-1876. DOI: 10.3969/j.issn.1000-8179.2012.23.002 |
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| Authors: | Zehao ZHUANG Fengxia WANG Jingjing WEI Jingwen SUN Fangming ZOU Liyong YANG |
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| Affiliation: | ①.Department of Gastroenterology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China②.Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou 350004, China |
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| Abstract: | Objective In a previous study, we found that low doses of cyclooxygenase-2 (COX-2) selective inhibitors could induce the proliferation of esophageal squamous cell carcinoma (ESCC) cells, which can be attributed to the activation of a 5-lipoxygenase (5-LOX) shunt by slight COX-2 inhibition. The objective of the present study was to determine whether highly effective COX-2 siRNA inhibition can avoid this shunt. Methods TE-1 and Eca109 (ESCC) cells were divided into blank control, liposome transfection, random sequence siRNA, and COX-2 siRNA groups. Cell proliferation was assessed using Cell Counting Kit-8 assay. Protein and mRNA expressions were determined using Western blot analysis and RT-PCR, respectively. Prostaglandin E2 and leukotriene B4 (LTB4) levels were measured by enzyme-linked immunosorbent assay. A flow cytometer was used for cell cycle measurement. Results Compared with the blank controls, COX-2 siRNA-transfected TE-1 and Eca109 cells showed 79% and 73% inhibition of COX-2 expression, respectively, as well as 45.86% and 48.99% inhibition of cell proliferation, respectively (P < 0.05). The expression of 5-LOX remained unchanged (P>0.05), and prostaglandin E2 and LTB4 levels were highly in accordance with alterations in COX-2 and 5-LOX expressions, respectively. The percentages of cells in G1 stage increased significantly. Bcl-2 expression decreased, whereas the expressions of caspase-9 and Bax increased in the two ESCC cells after COX-2 siRNA transfection (P < 0.05). Conclusions Highly effective inhibition of COX-2 expression may prevent the activation of 5-LOX and the following up-regulation of LTB4, which is a cell proliferation factor. These suggest that only high-dose COX-2 selective inhibitors with significant COX-2 inhibitory effects can achieve anti-cancer effects in ESCCs. |
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