Inhibition of cell growth and cell invasion by PPAR gamma in GI cancers

PPAR gamma 抑制胃肠道癌症中的细胞生长和细胞侵袭

• 批准号: 16590568
• 负责人: OKUMURA Toshikatsu
• 金额: $ 2.3万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590568/
• 关键词: troglitazone; extracellular signal releted kinase; mitogen-activated protein kinase kinase; pancreatic cancer cells; growth inhibition; PPARγ; 細胞増殖抑制; アポトーシス; アオトーシス

In the present study, we examined a role of mitogen-activated protein kinases (MAPKs), extracellular signal releted kinase (ERK), c-Jun N-terminal protein kinase (JNK) and p38 MAPK in troglitazone-induced inhibition of cell growth in human pancreatic cancer cells. Among the three kinases, troglitazone specifically inhibited the phosphorylation of ERK1/2 in a dose- and time-dependent manner. Troglitazone also down-regulated the protein expression of mitogen-activated protein kinase kinase (MEK)1/2, an upstream molecule that regulates ERK phosphorylation. Treatment of human pancreatic cancer cells with specific MEK inhibitor, PD98059 or U0126 inhibited ERK1/2 phosphorylation and cell growth. These results suggest for the first time that the inhibition of the MEK1/2-ERK1/2 signaling pathway may be implicated in the growth inhibitory effect by troglitazone in human pancreatic cancer cells.

在本研究中，我们研究了丝裂原活化蛋白激酶（MAPK），细胞外信号转导激酶（ERK），c-Jun N-末端蛋白激酶（JNK）和p38 MAPK在曲格列酮诱导的人胰腺癌细胞生长抑制中的作用。在这三种激酶中，曲格列酮以剂量和时间依赖性方式特异性抑制ERK 1/2的磷酸化。曲格列酮还下调了丝裂原活化蛋白激酶激酶（MEK）1/2的蛋白表达，MEK 1/2是一种调节ERK磷酸化的上游分子。用特异性MEK抑制剂PD 98059或U 0126处理人胰腺癌细胞可抑制ERK 1/2磷酸化和细胞生长。这些结果首次表明，MEK 1/2-ERK 1/2信号通路的抑制可能与曲格列酮在人胰腺癌细胞中的生长抑制作用有关。

项目成果

Increased expression of PPARg in high fat diet-induced liver steatosis in mice.

高脂饮食诱导的小鼠肝脏脂肪变性中 PPARg 表达增加。

• 发表时间: 2005
• 期刊: Biochem Biophys Res Commun 336
• 作者: Inoue M;et al.
• 通讯作者: et al.

Up-regulation of ADRP in fatty liver in human and liver steatosis in mice fed with high fat diet

• DOI: 10.1016/j.bbrc.2005.12.121
• 发表时间: 2006-02-24
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Motomura, W;Inoue, M;Okumura, T
• 通讯作者: Okumura, T

Growth arrest by troglitazone is mediated by p27^<Kip1> accumulation which is resulted from dual inhibition of proteasome activity and Skp2 expression in human hepatocellular carcinoma cells.

曲格列酮的生长停滞是通过 p27^<Kip1> 积累介导的，这是由于人肝细胞癌细胞中蛋白酶体活性和 Skp2 表达的双重抑制所致。

• 发表时间: 2004
• 期刊: Int J Cancer 108
• 作者: Motomura W;et al.
• 通讯作者: et al.

Activation of p38 mitogen-activated protein kinase is necessary for gemcitabine-induced cytotoxicity in human pancreatic cancer cells.

• 发表时间: 2005-09
• 期刊: Anticancer research
• 影响因子: 2
• 作者: K. Koizumi;S. Tanno;Y. Nakano;Atsuya Habiro;T. Izawa;Y. Mizukami;T. Okumura;Y. Kohgo

Inhibition of cell invasion and morphological change by troglitazone in cultured human pancreatic cancer cells.

曲格列酮对培养的人胰腺癌细胞的细胞侵袭和形态变化的抑制作用。

• 发表时间: 2004
• 期刊: J Gastroenterol 39
• 作者: Motomura W;et al.
• 通讯作者: et al.