文档介绍：福建医科大学
硕士学位论文
全反式维甲酸通过ERK1/2信号通路抑制结肠癌细胞增殖
姓名:陈艳
申请学位级别:硕士
专业:病理学与病理生理学
指导教师:殷平
2011-05
全反式维甲酸通过 ERK1/2 信号途径抑制结肠癌细胞的增殖
中文摘要
研究背景和目的:结肠癌是消化道常见的恶性肿瘤,大约 50%结肠癌发生与 Ras
基因突变有关。大量研究表明 Ras-MEK1/2-ERK1/2 信号途径在多种肿瘤(包括
结肠癌)的发生、发展及转移过程中处于异常活化状态。维甲酸(retinoi acid)
属于维生素 A 类化合物家族,因为羧基方向不同而分为两种异构体,即全反式
维甲酸(ATRA)和顺式维甲酸。ATRA 能够诱导多种肿瘤细胞分化或抑制肿瘤
细胞的增殖。故而本次实验旨在探讨全反式维甲酸(ATRA)是否通过作用
ERK1/2 信号通路抑制结肠癌细胞增殖及可能的分子机制。
方法:MTT 法检测示 ATRA 能够抑制结肠癌细胞增殖,RT-PCR 及 Western Blot
法检测经 ATRA 处理的结肠癌 LS174T 细胞中 MEK1/2-ERK1/2 的表达水平。流
式细胞仪测定 LS174T 细胞经 ATRA 与 PD98059(MEK1/2 的特异性抑制剂)联
合处理后的凋亡水平。
结果:MTT 法检测示 ATRA 抑制结肠癌细胞增殖;RT-PCR 及 Western Blot 法示
ATRA 能提高 LS174T 细胞中 ERK2 mRNA 水平,增强 MEK/ERK 蛋白表达,促
进 ERK 磷酸化。PD98059 与 ATRA 联用,部分降低结肠癌细胞 p-ERK 表达,
PD98059 部分增强 ATRA 诱导结肠癌细胞凋亡作用。
结论:ATRA 可以抑制结肠癌细胞增殖,其对肿瘤的诱导凋亡作用可能是通过包
含 MEK/ERK 信号途径在内的多条信号通路进行的。

关键词:全反式维甲酸细胞外信号调节蛋白激酶 PD98059 结肠肿瘤

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Abstract
All-trans retinal acid(ATRA) inhibits the proliferation of colonal
cancer through extracellular signal regulated kinase(ERK1/2) signal
pathway
Background and Purposes:Colonal cancer is mon digestive tract malignant
tumor,almost 50% are relevant with a ic mutation in the ras. Numerous studies
show that Ras-MEK1/2-ERK1/2 signaling are abnormal activated during the develop-
ment and metastasis of a variety of tumor(include colonal cancer). Retinoic acid
belongs to the family of Vitamin A, with the different COOH direction which are
divided into two isomers, that is all-trans retinoic acid (ATRA) and cis-retinoic acid.
Cell differentiation or growth inhibition of a lot of tumor can be induced by ATRA.
Therefore this study was to illustrate whether the growth of colonal cancer cells are
suppressed through extracellular signal regulated kinase (ERK1/2) signal pathway in
response to all-trans retinoic acid (ATRA) treatment.
Method:We observed the proliferation of the LS174Tcolonal cancer cells by MTT
assay; The expression of MEK/ERK in LS174T colonal c