吲哚美辛对结肠癌细胞系细胞周期蛋白的影响。
Effect of indomethacin on cell cycle proteins in colon cancer cell lines.
作者信息
Xu Mei-Hua, Zhang Gui-Ying
机构信息
Department of Gastroenterology, Xiangya Hospital, Central South University, 141 Xiangya Road, Changsha 410008, Hunan Province, China.
出版信息
World J Gastroenterol. 2005 Mar 21;11(11):1693-6. doi: 10.3748/wjg.v11.i11.1693.
AIM
To study the effect of indomethacin (IN) on human colon cancer cell line SW480 with p53 mutant and SW480 transfected wild-type p53 (wtp53/SW480) in vitro and investigate molecular mechanism of anti-tumor effect of IN on colon cancer.
METHODS
SW480 cells and wtp53/SW480 cells were treated with different concentrations of IN respectively, the expressions of CDK2, CDK4 and p21WAF1/CIP1 protein were detected by Western blotting.
RESULTS
IN gradually down-regulated the expression of CDK2, CDK4 protein of wtp53/SW480 cells in a dose-dependent manner, and inhibitory effect reached the maximum level at 600 micromol/L; IN up-regulated the expression of p21 WAF1/CIP1 protein in a dose-dependent manner at a certain concentration range, and the expression reached the maximum level at 400 micromol/L, and returned to the base level at 600 micromol/L. The expression of CDK2, CDK4 and p21WAF1/CIP1 protein of SW480 cells did not change.
CONCLUSION
IN exerts antitumor effect partly through down regulation of the expression of CDK2, CDK4 protein and up regulation of the expression of p21WAF1/PIC1.
目的
研究吲哚美辛（IN）对p53基因发生突变的人结肠癌细胞系SW480及转染野生型p53（wtp53/SW480）的SW480细胞的体外作用，探讨IN对结肠癌抗肿瘤作用的分子机制。
方法
分别用不同浓度的IN处理SW480细胞和wtp53/SW480细胞，采用蛋白质免疫印迹法检测细胞周期蛋白依赖性激酶2（CDK2）、细胞周期蛋白依赖性激酶4（CDK4）及p21WAF1/CIP1蛋白的表达。
结果
IN可使wtp53/SW480细胞中CDK2、CDK4蛋白表达呈剂量依赖性逐渐下调，600 μmol/L时抑制作用达最强；在一定浓度范围内，IN可使p21WAF1/CIP1蛋白表达呈剂量依赖性上调，400 μmol/L时表达达最高，600 μmol/L时恢复至基础水平。SW480细胞中CDK2、CDK4及p21WAF1/CIP1蛋白表达无变化。
结论
IN可能通过下调CDK2、CDK4蛋白表达及上调p21WAF1/CIP1蛋白表达发挥抗肿瘤作用。
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