Anti-tumor effectof 15d-PGJ2 on human hepatoma cells

15d-PGJ2对人肝癌细胞的抗肿瘤作用

• 批准号: 15590660
• 负责人: NAKAO Kazuhiko
• 金额: $ 1.86万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15590660/
• 关键词: 15d-PGJ2; TRAIL; TNF-α; hepatoma; NF-κB; STAT3

15d-PGJ2,a natural ligand of PPAR-γ, plays a key role in the differentiation of adipocytes and inhibits the cytokine-mediated NF-κB activation in various kinds of cells. Recently, it has been reported that 15d-PGJ2 has an anti-tumor activity in certain cancer cells. Therefore, in the present study, we evaluated the anti-tumor effect of 15d-PGJ2 on human hepatoma cells. 15d-PGJ2 inhibited the growth of HuH-7 human hepatoma cells in a dose-dependent manner. The cell cycle analysis revealed that 15d-PGJ2 induced G1 cell cycle arrest and small amounts of apoptosis in HuH-7 cells. Western blotting showed that 15d-PGJ2 down regulated the expression of cyclin D1,c-myc, Bcl-xL and survivin which are key molecules of growth and survival of cells, and inhibited the constitutive activation of STAT-3 in HuH-7 cells. In addition, pre-treatment of HuH-7 cells with 15d-PGJ2 greatly enhanced the Tumor necrosis factor(TNF)-related apoptosis-inducing ligand(TRAIL)-mediated apoptosis of these cells, in which TRAIL-induced NF-κB activation was dramatically repressed. These results suggest that 15d-PGJ2 has an anti-tumor activity against hepatoma cells through repressing both survival and growth signals of these cells

15d-PGJ2是PPAR-γ的天然配体，在脂肪细胞分化中起关键作用，抑制多种细胞因子介导的NF-κB活化。最近有报道称15d-PGJ2对某些癌细胞具有抗肿瘤活性。因此，在本研究中，我们评估了15d-PGJ2对人肝癌细胞的抗肿瘤作用。15d-PGJ2抑制HuH-7人肝癌细胞生长呈剂量依赖性。细胞周期分析显示，15d-PGJ2诱导HuH-7细胞G1周期阻滞和少量凋亡。Western blotting结果显示，15d-PGJ2下调细胞生长和存活的关键分子cyclin D1、c-myc、Bcl-xL和survivin的表达，抑制HuH-7细胞STAT-3的组成性激活。此外，15d-PGJ2预处理HuH-7细胞可显著增强肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）介导的细胞凋亡，其中TRAIL诱导的NF-κB活化被显著抑制。这些结果表明，15d-PGJ2通过抑制肝癌细胞的生存和生长信号而具有抗肿瘤活性

项目成果

Interferon-α sensitizes human hepatoma cells to TRAIL-induced apoptosis through DR5 upregulation and NF-κB inactivation

• DOI: 10.1038/sj.onc.1206139
• 发表时间: 2003-03-20
• 期刊: ONCOGENE
• 影响因子: 8
• 作者: Shigeno, M;Nako, K;Eguchi, K
• 通讯作者: Eguchi, K

Interferon alpha inhibits the nuclear factor kappa B activation triggered by X gene product of hepatitis B virus in human hepatoma cells.

干扰素α抑制人肝癌细胞中乙型肝炎病毒X基因产物触发的核因子κB激活。

• 发表时间: 2003
• 期刊: FEBS Lett. 553(3)
• 作者: Kazuyuki Ohata;et al.
• 通讯作者: et al.

Masaya Shigeno, et al.: "Interferon-α sensitizes human hepatoma cells to TRAIL-induced apoptosis through DR5 upregulation and NF-κB inactivation"Oncogene. 22(11). 1653-1662 (2003)

Masaya Shigeno 等人：“干扰素-α 通过 DR5 上调和 NF-κB 失活使人肝癌细胞对 TRAIL 诱导的细胞凋亡敏感”Oncogene 22(11)。

Kazuyuki Ohata, et al.: "Interferon alpha inhibits the nuclear factor kappa B activation triggered by X gene product of hepatitis B virus in human hepatoma cells"FEBS Lett.. 553(3). 304-308 (2003)

Kazuyuki Ohata 等人：“干扰素 α 抑制人肝癌细胞中由乙型肝炎病毒 X 基因产物触发的核因子 kappa B 激活”FEBS Lett.. 553(3)。

Antiangiogenic property of pigment epithelium-derived factor in hepatocellular carcinoma

• DOI: 10.1002/hep.20259
• 发表时间: 2004-07-01
• 期刊: HEPATOLOGY
• 影响因子: 13.5
• 作者: Matsumoto, K;Ishikawa, H;Eguchi, K
• 通讯作者: Eguchi, K