Lipopolysaccharide supports maintaining the stemness of CD133+ hepatoma cells through activation of the NF-κB/HIF-1α pathway
Lipopolysaccharide supports maintaining the stemness of CD133+ hepatoma cells through activation of the NF-κB/HIF-1α pathway
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脂多糖通过激活 NF-kappa B/HIF-1 α 通路支持维持 CD133( ) 肝癌细胞的干性
DOI：
10.1016/j.canlet.2016.05.014
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发表时间：
2016-08-10
期刊：
影响因子：
9.7
通讯作者：
Wei, Li-Xin
中科院分区：
文献类型：
--
作者：
Lai, Fo-Bao;Liu, Wen-Ting;Wei, Li-Xin
由于肿瘤干细胞（CSCs）的存在，人类肝细胞癌（HCC）在接受现有抗癌治疗后持续和复发是常见的。越来越多的证据表明，脂多糖（LPS）在HCC的恶化中起着至关重要的作用，但关于脂多糖对HCC的CSCs的影响的信息仍然很少。在这里，我们报道了从人HCC细胞系Huh7中分离出来的CD133(+) CSCs在LPS培养下保持良好的严肃性。在LPS的作用下，培养的CSCs中CD133表达的减少要小得多。在LPS刺激下，CSCs的克隆发生和肿瘤发生活性增加。LPS还支持维持CSC的迁移、侵袭和耐药能力。用HIF-1 α特异性siRNA治疗可显著降低CSCs在mRNA和蛋白水平上的CD133表达。此外，在lps刺激的CSCs中加入nf - κ B抑制剂后，HIF-1 α和CD133的表达降低。HIF-1 α特异性siRNA也能有效抵消LPS对维持CSC迁移和侵袭能力的影响。这些数据表明，肝肿瘤微环境中的重要介质LPS通过NF-kappa B/ HIF-1 α信号通路支持CSC严重度的维持。我们目前的研究强调，在HCC治疗过程中，LPS是开发新的治疗方法来消除CSCs的潜在靶点。2016爱思唯尔爱尔兰有限公司版权所有。
Due to the existence of cancer stem cells (CSCs), persistence and relapse of human hepatocellular carcinoma (HCC) are common after treatment with existing anti-cancer therapies. Emerging evidence indicates that lipopolysaccharide (LPS) plays a crucial role in aggravating HCC, but information about the effect of LPS on CSCs of HCC remains scant. Here, we report that the sternness of CD133(+) CSCs sorted from the human HCC cell line Huh7 was maintained well when cells were cultured with LPS. The reduction of CD133 expression was much lesser in cultured CSCs in the presence of LPS. In response to LPS stimulation, CSCs showed an increase in their activity of clonogenesis and tumorigenesis. LPS also supported maintaining CSC abilities of migration, invasion, and chemo-resistance. Treatment with HIF-1 alpha-specific siRNA significantly reduced CD133 expression by CSCs at both mRNA and protein levels. Further, the expression of HIF-1 alpha and CD133 was reduced in LPS-stimulated CSCs when the NF-kappa B inhibitor was added to the cell culture. HIF-1 alpha-specific siRNA also effectively counteracted the effect of LPS on maintaining CSC abilities of migration and invasion. These data indicate that LPS, an important mediator in the liver tumor microenvironment, supports the maintenance of CSC sternness through signaling of the NF-kappa B/ HIF-1 alpha pathway. Our current study highlights LPS as a potential target for developing new therapeutic approaches to eliminate CSCs during the treatment of HCC. (C) 2016 Elsevier Ireland Ltd. All rights reserved.