Effect of ligand troglitazone on peroxisome proliferator-activated receptor gamma expression and cellular growth in human colon cancer cells.
Effect of ligand troglitazone on peroxisome proliferator-activated receptor gamma expression and cellular growth in human colon cancer cells.
复制标题
配体曲格列酮对人结肠癌细胞中过氧化物酶体增殖物激活受体γ表达和细胞生长的影响。
作者：
Mei Ming;Jie;Xiang;Yan;Hong;He
目的
研究曲格列酮对人结肠癌HCT-116和HCT-15细胞增殖物激活受体γ（PPARgamma）表达及细胞生长的影响，并探讨其分子机制。
方法
用曲格列酮处理体外培养的人结肠癌HCT-116和HCT-15细胞。逆转录-聚合酶链反应（RT-PCR）和Western blot检测曲格列酮对PPARgamma表达的影响。MTT法检测细胞增殖活性，流式细胞仪检测细胞周期和凋亡。RT-PCR检测凋亡相关基因，Western blot检测细胞周期调控基因和p53蛋白。
结果
曲格列酮可上调结肠癌HCT-116和HCT-15细胞中PPARgamma的表达。曲格列酮抑制结肠癌细胞增殖，诱导细胞凋亡和细胞周期G1期阻滞。曲格列酮可诱导HCT-116细胞p53蛋白表达，但对HCT-15细胞无诱导作用。Survivin和bcl-2在两种细胞系中均表达下调，而bax仅在HCT-116细胞中表达上调，这与HCT-116细胞的生长抑制一致，而与HCT-15细胞的生长抑制无关。曲格列酮可增加HCT-116细胞中p21（WAF 1/CIP 1）（p21）、p27（KIP 1）（p27）的表达，并降低细胞周期蛋白D1的表达，而HCT-15细胞中仅发现细胞周期蛋白D1的轻微降低。
结论
曲格列酮是结肠癌细胞中的一种诱导剂，并可抑制PPAR γ依赖性增殖，这可能是结肠癌细胞中细胞周期G1阻滞和凋亡的原因。曲格列酮可诱导p53非依赖性细胞凋亡和p53依赖性p21和p27表达。根据细胞背景，结肠癌细胞中可能存在不同的激活途径。
AIM
To investigate the effect of troglitazone on pe-roxisome proliferator-activated receptor gamma (PPARgamma) expression and cellular growth in human colon cancer HCT-116 and HCT-15 cells and to explore the related molecular mechanism.
METHODS
Human colon cancer HCT-116 and HCT-15 cells cultured in vitro were treated with troglitazone. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot were employed to detect the effect of troglitazone on PPARgamma expression. The proliferative activity was determined by MTT assay, cell cycle and apoptosis were detected by flow cytometry. Apoptosis-related genes, cell cycle regulatory genes and p53 were examined by RT-PCR and Western blot respectively.
RESULTS
The expression of PPARgamma in colon cancer HCT-116 and HCT-15 cells was up-regulated by troglitazone. Troglitazone inhibited proliferation, induced apoptosis and cell cycle G1 arrest in colon cancer cells. Troglitazone induced p53 expression in HCT-116 cells, but not in HCT-15 cells. The down-regulation of survivin and bcl-2 was found in both cell lines and up-regulation of bax was found only in HCT-116 cells, being consistent with growth inhibition in HCT-116 cells but not in HCT-15 cells. Troglitazone increased expression of p21(WAF1/CIP1) (p21), p27(KIP1) (p27) and reduced cyclin D1 in HCT-116 cells while only a minor decrease of cyclin D1 was found in HCT-15 cells.
CONCLUSION
Troglitazone is an inductor of PPARgamma in colon cancer cells and inhibits PPARgamma-dependently proliferation, which may attribute to cell cycle G1 arrest and apoptosis in colon cancer cells. Troglitazone may induce p53-independent apoptosis and p53-dependent expression of p21 and p27. Depending on cell background, different activation pathways may exist in colon cancer cells.
影响因子：
11.2
作者：
C. Sherr
通讯作者：
C. Sherr
野生型 p53 在人结肠癌细胞系中表现出功能优势，可诱导可逆性生长停滞。
DOI：
--
发表时间：
1996
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research.
影响因子：
--
作者：
Yang,B;Stambrook,PJ;Markowitz,SD
通讯作者：
Markowitz,SD
DOI：
--
发表时间：
2003
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
S. Baek;Leigh C. Wilson;L. Hsi;T. Eling
通讯作者：
S. Baek;Leigh C. Wilson;L. Hsi;T. Eling