Role of activin A in induction of growth arrest and apoptosis by butyrate in colon cancer cells

激活素 A 在丁酸盐诱导结肠癌细胞生长停滞和凋亡中的作用

基本信息

批准号：
13660114
负责人：
SONOYAMA Kei
金额：
$ 2.62万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13660114/
关键词：
Activin A Butyrate Colorectal cencer HT-29 Smad IEC-6 ビタミンD

项目摘要

1. Colorectal tumor-suppressing effect of dietary fiber has been reportedly associated with its fermentation product butyrate. The present study investigated whether activin A mediates butyrate-induced growth arrest and apoptosis in colon cancer cells.2. Butyrate induced G1 arrest and apoptosis in human colon cancer cell line HT-29. Butyrate also stimulated activin A gene in time-and dose-dependent manner. Because trichostain A also stimulated activin A gene, the effect of butyrate is possibly associated with the inhibition of histone acetylase. Stimulation of activin A gene by butyrate seems to be specific to cancer cells, as normal cell lines showed no response to butyrate.3. Exogenous activin A did not aggect the growth of HT-29 cells. Immuneprecipitation coupled with Western blotting revealed that activin A induced phosphorylation of smad2 but not complex formation of smad2/3/4 in HT-29 cells. The cell line expressed neither smad4 mRNA nor protein. It is thus suggested that unresponsiveness to activin A in HT-29 cells is due to mutation of smad4.4. Taken together, upregulated activin A by butyrate in colon cancer cells acts as paracrine factor rather than autocrine factor. Thus activin A does not mediate butyrate-induced growth arrest and apoptosis in colon cancer cells.

1。据报道，饮食纤维的结直肠肿瘤抑制作用与其发酵产物丁酸酯有关。本研究调查了活化素是否介导丁酸酯诱导的结肠癌细胞中的生长停滞和凋亡。2。丁酸酯诱导人类结肠癌细胞系HT-29中的G1停滞和凋亡。丁酸酯还以时间和剂量依赖性方式刺激了一个基因。由于Trichostain A也刺激了激活素A基因，因此丁酸酯的作用可能与组蛋白乙酰酶的抑制有关。丁酸酯对刺激素A基因的刺激似乎是癌细胞的特异性，因为正常细胞系对丁酸酯没有反应。3。外源激活素A没有促进HT-29细胞的生长。免疫沉淀加上蛋白质印迹表明，激活素A诱导的Smad2磷酸化，但在HT-29细胞中Smad2/3/4的磷酸化并不复杂。细胞系既不表达SMAD4 mRNA也不蛋白质。因此，提出，HT-29细胞中对激活素A的反应性是由于Smad4.4的突变引起的。综上所述，在结肠癌细胞中丁酸酯上调了AIVICIN A充当旁分泌因子，而不是自分泌因子。因此，激活素A不介导丁酸诱导的结肠癌细胞中的生长停滞和凋亡。