Combination of 5-fluorouracil and 2-morphilino-8-phenyl-4H-chromen-4-one may inhibit liver cancer stem cell activity
Combination of 5-fluorouracil and 2-morphilino-8-phenyl-4H-chromen-4-one may inhibit liver cancer stem cell activity
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5-氟尿嘧啶和2-吗啉基-8-苯基-4H-chromen-4-one组合可能抑制肝癌干细胞活性
DOI：
10.1007/s13277-016-4915-3
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发表时间：
2016-02
期刊：
影响因子：
--
通讯作者：
Li, Le-Qun
中科院分区：
文献类型：
--
作者：
Xie, Zhi-Bo;You, Xue-Mei;Peng, Ning-Fu;Li, Le-Qun
本工作旨在评价2-吗啉-8-苯基-4H-色曼-4-酮(LY294002)联合5-氟尿嘧啶(5-FU)对人肝癌细胞系MHCC97H来源的CD90+肝癌细胞活性的影响。在无血清条件下扩增MHCC97H球体形成细胞(MSFCs)，用流式细胞仪从MSFCs中分离CD90+细胞。这些CD90+细胞的表型显示了肝癌干细胞的行为，在体外和裸鼠异种移植模型中得到了验证。将未用药、LY294002单独、5-FU单独或联合用药处理MSFC、CD90+肝癌细胞(CD90+LCC)和亲代MHCC97H细胞，然后比较干细胞相关基因的表达、增殖和侵袭能力。干细胞表型随CD90+细胞比例增加而增加，由高到低依次为：亲代MHCC97H细胞、MSFCs、CD90+肝癌细胞。LY294002以浓度依赖的方式抑制CD90+LCC和MSFC中CD90、Nanog、SALL4和SHP2的表达，但对亲代细胞无明显影响。LY294002通过PI3K/AKT信号通路阻断AKT的磷酸化，抑制CD90+LCC的增殖和体内致瘤性。CD90+肝癌细胞可表达肝癌干细胞表型。在本研究中，LY294002抑制MHCC97H来源的CD90+LCC的增殖和侵袭，并增敏CD90+LCC来源的肿瘤细胞对5-FU的敏感性，这可能为深入了解LY294002联合5-FU与肝癌干细胞(LSCs)之间的关系提供依据。
This work aims to evaluate the impact of 2-morpholino-8-phenyl-4H-chromen-4-one (LY294002) combined 5-fluorouracil (5-FU) for the activity of CD90+ liver cancer cells derived from the human liver cancer cell line MHCC97H. MHCC97H sphere-forming cells (MSFCs) were amplified in serum-free medium and CD90+ cells were isolated from bulk MSFCs using flow cytometry. The phenotype of these CD90+ cells which show liver cancer stem cells (LCSCs) behavior was validated in vitro and in a xenograft model in nude mice. MSFCs, CD90+ liver cancer cells (CD90+ LCCs), and parental MHCC97H cells were treated with no drug, LY294002 alone, 5-FU alone, or both drugs together and then compared in terms of stem cell-related gene expression, proliferation, and invasion. Stem cell phenotype increased with increasing proportion of CD90+ cells, in ascending order: parental MHCC97H cells, MSFCs, and CD90+ liver cancer cells. LY294002 reduced the expression of CD90, Nanog, SALL4, and SHP2 in a concentration-dependent manner in CD90+ LCCs and MSFCs, but not in parental cells. LY294002 blocked AKT phosphorylation via the PI3K/AKT signaling pathway and inhibited CD90+ LCCs proliferation and tumorigenicity in vitro and in vivo. CD90+ liver cancer cells can express liver cancer stem cell phenotype. LY294002 inhibits the proliferation and invasion of MHCC97H-derived CD90+ LCCs and sensitized CD90+ LCCs-derived tumors to 5-FU in the current study which may provide insight into the association between the LY294002 combined 5-FU and liver cancer stem cell (LCSCs).
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影响因子：
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作者：
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