Resveratrol Suppresses Lung Cancer by Targeting Cancer Stem-Like Cells and Regulating Tumor Microenvironment.
Resveratrol Suppresses Lung Cancer by Targeting Cancer Stem-Like Cells and Regulating Tumor Microenvironment.
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DOI：
10.1016/j.jnutbio.2022.109211
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发表时间：
2022-11
期刊：
影响因子：
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通讯作者：
Chun-feng Xie;C. Liang;Rong Wang;Kefan Yi;Xu Zhou;Xiao-ting Li;Yue Chen;D. Miao;Cai-yun Zhong;Jian-yun Zhu
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文献类型：
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作者：
Chun-feng Xie;C. Liang;Rong Wang;Kefan Yi;Xu Zhou;Xiao-ting Li;Yue Chen;D. Miao;Cai-yun Zhong;Jian-yun Zhu
越来越多的证据表明，癌症干细胞（CSC）是肿瘤发生和复发的关键驱动因素。肿瘤微环境（TME）的细胞和可溶性组分影响癌症的发生和进展，如细胞因子和趋化因子。因此，靶向CSC和TME是一种新的抗癌方法。白藜芦醇（RES）是从多种植物中提取的具有生物活性的植物化学物质，在肺癌中表现出抑制肿瘤的活性，但其机制仍然知之甚少。我们的数据显示，IL-6的表达水平与人肺癌组织中肺癌干细胞样细胞（LCSCs）的存在呈正相关，体外实验结果显示，IL-6在肺癌球形成细胞中高度升高，并可增强LCSCs的干细胞性，包括肿瘤球形成能力、CD 133阳性细胞百分比、以及LCSC特异性标志物（CD 133、ALDH 1A 1和Nanog）的表达。同时，我们的研究结果证实RES能有效抑制LCSC的特性，下调Wnt/β-catenin信号通路，降低IL-6水平。此外，我们发现RES处理减弱了LiCl（GSK 3 β激动剂）对Wnt/β-catenin信号传导的激活。IL-6促进的LCSC特性和Wnt/β-catenin信号也被RES逆转。总之，这些数据表明RES通过靶向TME中的LCSC和IL-6来抑制肺癌。这项研究的新发现提供了证据，表明RES在抑制肺癌方面具有多靶点作用，可能是一种新的有效的癌症预防化合物。
Increasing evidence indicate that cancer stem cells (CSCs) are the key driver of tumor initiation and recurrence. The cellular and soluble components of the tumor microenvironment (TME) impact on cancer initiation and progression, such as cytokines and chemokines. Thus, targeting CSCs and TME is a novel anti-cancer approach. Resveratrol (RES), a bioactive phytochemical extracted from various plants, exhibits tumor-suppressing activities in lung cancer, yet the mechanism remains poorly understood. Our data showed that the expression level of IL-6 was positively correlated with the presence of lung cancer stem-like cells (LCSCs) in human lung cancer tissues.In vitroresults showed that IL-6 was highly elevated in lung cancer sphere-forming cells and could enhance the stemness of LCSCs, including tumor sphere formation ability, the percentage of CD133 positive cells, and the expression of LCSC specific markers (CD133, ALDH1A1 and Nanog). Simultaneously, our results confirmed that RES effectively inhibited LCSC properties, downregulated Wnt/β-catenin signaling and reduced IL-6 levelin vitroandin vivo. Furthermore, we found RES treatment attenuated the activation of Wnt/β-catenin signaling by LiCl (GSK3β agonist). IL-6-promoted LCSC properties and Wnt/β-catenin signaling was also reversed by RES. Taken together, these data illustrated that RES inhibited lung cancer by targeting LCSCs and IL-6 in TME. The novel findings from this study provided evidence that RES exhibited multi-target effects on suppression of lung cancer and could be a novel potent cancer-preventive compound.