EF24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma.
EF24 inhibits tumor growth and metastasis via suppressing NF-kappaB dependent pathways in human cholangiocarcinoma.
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EF24 通过抑制人胆管癌中的 NF-κB 依赖性途径来抑制肿瘤生长和转移。
DOI：
10.1038/srep32167
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发表时间：
2016-08-30
影响因子：
4.6
通讯作者：
Liu LX
中科院分区：
文献类型：
--
作者：
Yin DL;Liang YJ;Zheng TS;Song RP;Wang JB;Sun BS;Pan SH;Qu LD;Liu JR;Jiang HC;Liu LX
姜黄素的合成单酮类似物，称为3，5-双（2-氟苯亚甲基）哌啶-4-酮（EF 24），已报道在体外和体内抑制多种癌细胞的生长。然而，EF 24是否对胆管癌（CCA）细胞具有抗肿瘤作用及其机制仍有待研究。本研究的目的是探讨EF 24对CCA肿瘤生长和转移的抑制作用的分子机制。检测细胞增殖、凋亡、迁移、侵袭、成瘤和转移情况。EF 24对HuCCT-1、TFK-1和HuH 28人CCA细胞系表现出时间和剂量依赖性抑制作用。EF 24可抑制CCA细胞增殖、迁移，并诱导其阻滞于G2/M期。EF 24通过负调控NF-κB- X-linked inhibitor of apoptosis protein（XIAP）信号通路，沿着诱导细胞凋亡。慢病毒介导的RNA干扰抑制XIAP增强EF 24诱导的细胞凋亡，而XIAP过表达减少它在CCA细胞。在体内，EF 24显著抑制CCA肿瘤异种移植物的生长和肿瘤转移，同时显示低毒性水平。我们的研究结果表明，EF 24是一种有效的抗肿瘤剂，通过抑制NF-κB依赖的信号通路来抑制肿瘤生长和转移。EF 24可能代表CCA治疗的新方法。
A synthetic monoketone analog of curcumin, termed 3, 5-bis (2-flurobenzylidene) piperidin-4-one (EF24), has been reported to inhibit the growth of a variety of cancer cells both in vitro and in vivo. However, whether EF24 has anticancer effects on cholangiocarcinoma (CCA) cells and the mechanisms remain to be investigated. The aim of our study was to evaluate the molecular mechanisms underlying the anticancer effects of EF24 on CCA tumor growth and metastasis. Cell proliferation, apoptosis, migration, invasion, tumorigenesis and metastasis were examined. EF24 exhibited time- and dose-dependent inhibitory effects on HuCCT-1, TFK-1 and HuH28 human CCA cell lines. EF24 inhibited CCA cell proliferation, migration, and induced G2/M phase arrest. EF24 induced cell apoptosis along with negative regulation of NF-κB- X-linked inhibitor of apoptosis protein (XIAP) signaling pathway. XIAP inhibition by lentivirus mediated RNA interference enhanced EF24-induced apoptosis, while XIAP overexpression reduced it in CCA cells. In vivo, EF24 significantly suppressed the growth of CCA tumor xenografts and tumor metastasis while displaying low toxicity levels. Our findings indicate that EF24 is a potent antitumor agent that inhibits tumor growth and metastasis by inhibiting NF-κB dependent signaling pathways. EF24 may represent a novel approach for CCA treatment.
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影响因子：
2.3
作者：
Adams, BK;Cai, JY;Shoji, M
通讯作者：
Shoji, M
影响因子：
3.5
作者：
Adams, BK;Ferstl, EM;Shoji, M
通讯作者：
Shoji, M
影响因子：
3.6
作者：
Kasinski, Andrea L.;Du, Yuhong;Fu, Haian
通讯作者：
Fu, Haian
二苯基二氟酮：人类肝细胞癌的有效化疗候选物。
影响因子：
3.7
作者：
Liang Y;Yin D;Hou L;Zheng T;Wang J;Meng X;Lu Z;Song X;Pan S;Jiang H;Liu L
通讯作者：
Liu L
影响因子：
4.8
作者：
Gogada, Raghu;Prabhu, Varun;Chandra, Dhyan
通讯作者：
Chandra, Dhyan