Tectorigenin ablates the inflammation-induced epithelial-mesenchymal transition in a co-culture model of human lung carcinoma
Tectorigenin ablates the inflammation-induced epithelial-mesenchymal transition in a co-culture model of human lung carcinoma
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DOI：
10.1016/j.pharep.2014.10.020
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发表时间：
2015-04-01
影响因子：
4.4
通讯作者：
Qadri, Raies A.
中科院分区：
文献类型：
--
作者：
Amin, Asif;Mokhdomi, Taseem A.;Qadri, Raies A.
目的：肿瘤不仅能够从宿主免疫系统中逃脱，而且通过改变免疫细胞的功能，有效地从浸润的免疫细胞中获益，从而创造有利于肿瘤进展和转移的促炎微环境。在这项研究中，我们研究了鸢尾黄素是否可以抑制肺癌诱导的单核细胞的促炎反应。材料和方法：建立A549:THP1共培养模型，促进促炎细胞因子白介素(IL)-6和肿瘤坏死因子α (tnf - α)的释放。通过单核细胞的细胞因子释放和A549细胞的转移/上皮间质转化（EMT）监测鸢尾黄素对A549侵袭性表型的影响。结果：在接触A549:THP1共培养模型中，THP-1细胞被A549细胞激活，有利于促炎细胞因子、tnf - α和IL-6的分泌。然而，在A549细胞中注入鸢尾黄素24小时，THP-1细胞对A549细胞诱导的tnf - α和IL-6分泌有抑制作用。在接触共培养条件下，鸢尾黄素诱导的A549细胞功能表型变化使THP-1细胞对IL-6和tnf - α的分泌无反应。此外，这种无反应的A549:THP-1共培养的条件培养基抑制了A549细胞的转移潜力，伤口愈合和transwell迁移实验证实了这一点。这些发现进一步证实了Snail的表达减少，同时E-cadherin （EMT的两个标志性标志物）的表达增加。结论：这些结果清楚地证明了鸢尾黄素在预防肺癌引起的单核细胞炎症和促转移反应方面的治疗潜力，值得进一步研究以阐明其作用机制。(C) 2014年波兰科学院药理学研究所。Elsevier Urban & Partner Sp. z . oo出版，版权所有。
Objectives: Tumors not only manage to escape from the host immune system, but they effectively contrive to benefit from infiltrating immune cells by modifying their functions so as to create a proinflammatory microenvironment favorable for tumor progression and metastasis. In this study we investigated if tectorigenin could suppress lung cancer-induced pro-inflammatory response generated from monocytes.Materials and methods: A549:THP1 co-culture model was set-up favoring release of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor alpha (TNF-alpha). Effect of tectorigenin on A549 imparted invasive phenotype of A549:THP-1 co-culture was monitored by cytokine release from monocytes, and metastasis/epithelial-mesenchymal transitiom (EMT) in A549 cells.Results: In a contact A549:THP1 co-culture model, THP-1 cells were activated by A549 cells favoring secretion of pro-inflammatory cytokines, TNF-alpha and IL-6. However, priming of A549 cells with tectorigenin for 24 h repressed A549 cell-induced secretion of TNF-alpha and IL-6 by THP-1 cells. Tectorigenin induced change in functional phenotype of A549 cells rendered THP-1 cells non-responsive for the secretion of IL-6 and TNF-alpha in a contact co-culture setup. Additionally, conditioned media from this non-responsive A549:THP-1 co-culture suppressed metastatic potential of A549 cells as confirmed by the wound healing and transwell migration assays. These finding were further corroborated by decrease in expression of Snail with a concomitant increase in E-cadherin, the two signature markers of EMT.Conclusion: These results clearly demonstrate the therapeutic potential of tectorigenin to prevent lung cancer elicited inflammatory and pro-metastatic response in monocytes and warrants further investigations to elucidate its mechanism of action. (C) 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.