| 摘要: |
| 目的探讨环氧化酶2(COX-2)/前列腺素E2(PGE2)是否通过Wnt/β-catenin信号通路调控人肠癌细胞血管内皮生长因子(VEGF)的表达。方法将PGE2或COX-2选择性抑制剂NS-398作用LoVo细胞24 h,采用蛋白质印迹法检测COX-2和β-catenin蛋白表达；将PGE2 和(或)β-catenin/tcf抑制剂FH-535作用LoVo细胞24 h,采用ELISA法检测VEGF表达。以常规培养的LoVo细胞为对照。结果与对照组比较,PGE2能够上调LoVo细胞中COX-2蛋白表达,同时上调β-catenin在细胞总蛋白、细胞浆蛋白和核蛋白中的表达水平(分别是对照组的3.8倍、2.7倍和3.0倍,P均<0.01)；COX-2抑制剂能够下调COX-2蛋白表达,同时下调β-catenin在细胞总蛋白、细胞浆蛋白和核蛋白中的表达水平(分别是对照组的0.3倍、0.3倍和0.2倍,P均<0.01)。与对照组比较,PGE2能够上调LoVo细胞VEGF表达水平(是对照组的1.6倍,P<0.01)；β-catenin/tcf抑制剂能够下调VEGF表达(是对照组的0.68倍,P<0.01)；将PGE2和β-catenin/tcf抑制剂同时作用LoVo细胞后VEGF表达水平与对照组相比差异无统计学意义(P>0.05)。结论COX-2/PGE2通过上调β-catenin蛋白表达,从而激活Wnt/β-catenin信号通路,上调VEGF表达,这可能是COX-2/PGE2促进大肠癌血管新生的机制之一。 |
| 关键词: 结直肠肿瘤 环氧化酶2 Wnt/β-catenin信号通路 血管内皮生长因子 |
| DOI：10.3724/SP.J.1008.2012.001178 |
| 投稿时间：2012-07-27修订日期：2012-09-24 |
| 基金项目:上海市自然科学基金 (09ZR1428500)；上海市六院医疗集团项目(20114001)；上海市教委科研创新项目(12YZ058)；上海市普陀区科委重点项目(2010PTKW005). |
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| COX-2/PGE2 regulates VEGF expression by activating Wnt/β-catenin signal pathway in human colorectal cancer cells |
| LIU Xuan1,LI Dan-guang2,ZHOU Li-hong1,WANG Yan1,YIN Pei-hao1,JI Qing1,FAN Zhong-ze1,LI Qi1* |
(1. Department of Oncology, Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062,China
2. Department of Radiology, Jilin Provincial Cancer Hospital, Changchun 130012, Jilin, China
*Corresponding author.) |
| Abstract: |
| Objective To investigate whether COX-2/PGE2 can regulate vascular endothelial growth factor (VEGF) expression through activating Wnt/β-catenin signal pathway in human colorectal cancer cells. Methods PGE2 and (or) COX-2 selective inhibitor NS-398 was used to treat LoVo cells for 24 h, and then COX-2 and β-catenin protein expression was detected by Western blotting analysis. PGE2 and (or) β-catenin/tcf selective inhibitor FH-535 were used to treat LoVo cells for 24 h, and then the levels of VEGF was determined by ELISA. Routinely cultured LoVo cells were taken as control. Results Compared with the control group, PGE2 not only increased COX-2 protein expression, but also increased the levels of β-catenin in the total cell, cytosolic and nuclear proteins (being 3.8 folds, 2.7 folds, and 3.0 folds of the control, respectively, P<0.01). COX-2 selective inhibitor not only decreased COX-2 protein expression, but also decreased the levels of β-catenin in the total cell, cytosolic and nuclear proteins (being 0.3 folds, 0.3 folds, and 0.2 folds of the control, P<0.01). Compared with the control group, PGE2 increased VEGF expression in LoVo cells (being 1.6 folds of the control, P<0.01), and β-catenin/tcf selective inhibitor decreased VEGF expression in LoVo cells (being 0.68 folds of the control, P<0.01). Co-treatment of LoVo cells with β-catenin/tcf selective inhibitor and PGE2 showed no great effect on VEGF expression. Conclusion COX-2/PGE2 can increase β-catenin protein level, subsequently activate Wnt/β-catenin signal pathway and promote VEGF expression,which might be one of the mechanisms for COX-2/PGE2-induced angiogenesis in colon cancer. |
| Key words: colorectal neoplasms cyclooxygenase 2 Wnt/β-catenin signal pathway vascular endothelial growth factor |
