Antineoplastic effects of gamma linolenic Acid on hepatocellular carcinoma cell lines.

Antineoplastic effects of gamma linolenic Acid on hepatocellular carcinoma cell lines.
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DOI:
10.3164/jcbn.10-24
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发表时间:
2010-07
影响因子:
2.4
通讯作者:
Maehara Y
Maehara Y
中科院分区:
医学4区
文献类型:
--
作者:
Itoh S;Taketomi A;Harimoto N;Tsujita E;Rikimaru T;Shirabe K;Shimada M;Maehara Y

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本研究旨在探讨γ-亚麻酸(GLA)对人肝癌细胞株的作用及其机制。将人HCC细胞系HuH 7暴露于GLA。比较细胞增殖和活性氧(ROS)的产生,包括脂质过氧化和凋亡。然后,我们使用cDNA微阵列分析,以调查由GLA引起的分子变化。GLA处理显著降低细胞增殖,产生ROS,并诱导凋亡。Huh 7细胞暴露于GLA 24小时后,我们确定了几个编码上调的抗氧化蛋白的基因:血红素加氧酶-1(HO-1)、醛酮还原酶1家族C1(AKR 1C 1)、C4(AKR 1C 4)和硫氧还蛋白(Trx)。使用Western印迹分析,在GLA暴露后,HO-1蛋白水平在Huh 7细胞中过表达。此外,铬中卟啉(CrMP),HO活性的抑制剂,显着增强GLA的细胞毒性。GLA处理诱导细胞生长抑制、ROS产生(包括脂质过氧化)和HO-1产生,以对抗Huh 7细胞中GLA引起的氧化应激的抗氧化保护。GLA治疗应被视为晚期HCC患者的一种治疗方式。
The aim of this study was to investigate the effect and the mechanism of gamma linolenic acid (GLA) treatment on human hepatocellular (HCC) cell lines. The human HCC cell line HuH7 was exposed to GLA. Cell proliferation and reactive oxygen species (ROS) generation including lipid peroxidation and apoptosis were compared. We then used a cDNA microarray analysis to investigate the molecular changes induced by GLA. GLA treatment significantly reduced cell proliferation, generated ROS, and induced apoptosis. After 24 h exposure of Huh7 cells to GLA, we identified several genes encoding the antioxidant proteins to be upregulated: heme oxygenase-1 (HO-1), aldo-keto reductase 1 family C1 (AKR1C1), C4 (AKR1C4), and thioredoxin (Trx). The HO-1 protein levels were overexpressed in Huh7 cells after GLA exposure using a Western blot analysis. Furthermore, chromium mesoporphyrin (CrMP), an inhibitor of HO activity, significantly potentiated GLA cytotoxicity. GLA treatment has induced cell growth inhibition, ROS generation including lipid peroxidation, and HO-1 production for antioxidant protection against oxidative stress caused by GLA in Huh7 cells. GLA treatment should be considered as a therapeutic modality in patients with advanced HCC.
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发表时间: 2004-06-01
期刊: CANCER
影响因子: 6.2
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