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| 塞来昔布通过阻断丝裂原活化蛋白激酶信号途径抑制多囊肾囊肿衬里上皮细胞增殖 |
| 许涛,曲巍,梅长林,叶朝阳,王素霞,付莉莉,XUTao,QUWei,MEIChang-lin,YEChao-yang,WANGSu-xia,FULi-li |
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| 摘要: |
| 目的:探讨环氧合酶-2(COX-2)抑制剂塞来昔布(CXB)能否通过阻断丝裂原活化蛋白激酶(MAPK)信号转导途径抑制多囊肾囊肿衬里上皮细胞增殖.方法:原代培养多囊肾囊肿衬里上皮细胞,以不同浓度CXB(0、2.5 ×10-6、5×10-6、1×10-5、2×10-5、3×10-5、4×10-5、5×10-5mol/L)处理细胞,采用BrdU法检测细胞增殖状态.ELISA法检测各组血管内皮生长因子(VEGF)的含量.荧光定量PCR技术检测增殖细胞核抗原(PCNA)、磷酸化MAPK的mRNA含量,Western印迹法检测PCNA、MAPK和磷酸化MAPK的表达.结果:CXB对囊肿衬里上皮细胞的增殖具有明显抑制作用,呈时间和剂量依赖性,其中2×10-5mol/L CXB作用24 h的抑制作用最强,抑制率为(63.9±1.2)％;CXB可减少囊肿衬里上皮细胞VEGF的分泌,而且抑制作用具有时间、浓度依赖性.CXB剂量依赖性减低PCNA和磷酸化MAPK的mRNA和蛋白表达.结论:CXB明显抑制囊肿衬里上皮细胞增殖,抑制细胞产生VEGF;其作用与干扰MAPK磷酸化,部分阻断MAPK信号转导通路有关. |
| 关键词: 塞来昔布、丝裂原活化蛋白激酶、囊肿衬里上皮细胞、多囊肾,常染色体显性 |
| DOI：10.3724/SP.J.1008.2006.00585 |
| 投稿时间：2006-03-29修订日期：2006-05-20 |
| 基金项目:国家自然科学基金重点项目（30330640）;国家自然科学基金面上项目（30271523）;国家自然科学基金（30576867）. |
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| Celecoxib inhibits proliferation of polycystic kidney cyst lining epithelial cells through blocking mitogen-activated protein kinase signal transduction pathways |
| 许涛,曲巍,梅长林,叶朝阳,王素霞,付莉莉,XU Tao,QU Wei,MEI Chang-lin,YE Chao-yang,WANG Su-xia,FU Li-li |
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| Abstract: |
| Objective：To investigate whether celecoxib （CXB）, a specific COX-2 inhibitor, can inhibit the proliferation of cyst lining epithelial cells through blocking mitogen-activated protein kinase （MAPK） signal transduction pathway. Methods： Primarily cultured cells were treated with different concentrations of CXB （0,2.5 × 10^- 6 , 5 × 10^-6 , 1 × 10^-5 , 2 × 10^-5 , 3 × 10^-5 , 4 × 10^-5 ,5 × 10^-5 mol/L） and the proliferative status was evaluated by BrdU assay. The levels of vascular endothelial growth factor （VEGF） were measured by enzyme-linked immunosorbent assay （ELISA） ; the production of proliferating cell nuclear antigen （PCNA） and phospho-MAPK were measured by real-time reverse transcription-PCR assay;and the expression of PCNA, MAPK and phospho-MAPK protein was detected by Western blotting. Results： BrdU assay revealed that CXB inhibited cell growth in a concentration-dependent manner; the maximum inhibition rate （[63.9± 1.2] %） was found when cells were treated with 2± 10^-5 mol/L CXB for 24 h. VEGF secretion by cyst lining epithelial cell was reduced by CXB in a concentration and time-dependent manner. The mRNA and protein levels of PCNA, phospho-MAPK in CXB-treated group were lower than those in control group （with no CXB treatment）. Conclusion： CXB can obviously inhibit the proliferation of cyst lining epithelial cell and the secretion of VEGF, which might be through interfering with the phosphorylation of MAPK and partly blocking MAPK signal transduction pathway. |
| Key words: celecoxib mitogen-activated protein kinase cyst lining epithelial cell polycystic kidney,autosomal dominant |
