Rocaglamide overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in hepatocellular carcinoma cells by attenuating the inhibition of caspase-8 through cellular FLICE-like-inhibitory protein downregulation.
Rocaglamide overcomes tumor necrosis factor-related apoptosis-inducing ligand resistance in hepatocellular carcinoma cells by attenuating the inhibition of caspase-8 through cellular FLICE-like-inhibitory protein downregulation.
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Rocaglamide 通过下调细胞 FLICE 样抑制蛋白来减弱 caspase-8 的抑制，从而克服肝细胞癌细胞中肿瘤坏死因子相关的凋亡诱导配体耐药性
DOI：
10.3892/mmr.2014.2718
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发表时间：
2015-01
影响因子：
3.4
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Luan Z;He Y;He F;Chen Z
增强细胞凋亡是一种用于治疗癌症的治疗策略。肿瘤坏死因子相关凋亡诱导配体（TRAIL）是一种很有前途的抗肿瘤药物。然而，肝细胞癌（HCC）细胞对TRAIL诱导的细胞死亡表现出明显的抗性。本研究调查了从Aglaia属中分离的天然产物rocaglamide是否能够使耐药HCC细胞对trail介导的凋亡敏感。用rocaglamide和/或TRAIL处理两种HCC细胞系HepG2和Huh-7，研究其诱导凋亡和对TRAIL信号通路的影响。rocaglamide在trail耐药huh -7衍生肿瘤异种移植物中的体内疗效被确定。Rocaglamide显著使TRAIL-resistant HCC细胞对TRAIL凋亡敏感，这是由于Rocaglamide介导的细胞fliclike抑制蛋白下调和随后的caspase-8激活。此外，rocaglamide显著抑制了在严重联合免疫缺陷小鼠中增殖的Huh-7细胞的肿瘤生长，表明体内也发生了化学化。这些数据表明，rocaglamide与TRAIL协同作用，对抗TRAIL耐药的HCC细胞。因此，我们得出结论，rocaglamide作为基于trail的治疗的辅助治疗可能是治疗HCC的一种有希望的治疗方法。
The enhancement of apoptosis is a therapeutic strategy used in the treatment of cancer. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising antitumor agent. However, hepatocellular carcinoma (HCC) cells exhibit marked resistance to the induction of cell death by TRAIL. The present study investigated whether rocaglamide, a naturally occurring product isolated from the genus Aglaia, is able to sensitize resistant HCC cells to TRAIL-mediated apoptosis. Two HCC cell lines, HepG2 and Huh-7, were treated with rocaglamide and/or TRAIL and the induction of apoptosis and effects on the TRAIL signaling pathway were investigated. The in vivo efficacy of rocaglamide was determined in TRAIL-resistant Huh-7-derived tumor xenografts. Rocaglamide significantly sensitized the TRAIL-resistant HCC cells to apoptosis by TRAIL, which resulted from the rocaglamide-mediated downregulation of cellular FLICE-like inhibitory protein and subsequent caspase-8 activation. Furthermore, rocaglamide markedly inhibited tumor growth from Huh-7 cells propagated in severe combined immunodeficient mice, suggesting that chemosentization also occurred in vivo. These data suggest that rocaglamide acted synergistically with TRAIL against the TRAIL-resistant HCC cells. Thus, it is concluded that rocaglamide as an adjuvant to TRAIL-based therapy may present a promising therapeutic approach for the treatment of HCC.
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c-FLIP在人肝细胞癌中的表达及生物学意义
DOI：
10.1186/1756-9966-28-24
发表时间：
2009-02-20
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Du X;Bao G;He X;Zhao H;Yu F;Qiao Q;Lu J;Ma Q
通讯作者：
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通讯作者：
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Walczak, H
影响因子：
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作者：
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通讯作者：
Ashkenazi, Avi
影响因子：
6.6
作者：
Kunzi-Rapp, K;Genze, F;Gschwend, JE
通讯作者：
Gschwend, JE