Shikonin blocks human lung adenocarcinoma cell migration and invasion in the inflammatory microenvironment via the IL-6/STAT3 signaling pathway
Shikonin blocks human lung adenocarcinoma cell migration and invasion in the inflammatory microenvironment via the IL-6/STAT3 signaling pathway
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DOI：
10.3892/or.2020.7683
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发表时间：
2020-09-01
期刊：
影响因子：
4.2
通讯作者：
Ren, Xinling
中科院分区：
文献类型：
--
作者：
Pan, Tao;Zhang, Fang;Ren, Xinling
越来越多的证据表明，炎性肿瘤微环境可导致癌细胞转移。紫草素是从紫草中提取的，具有多种药理作用，但其在炎症微环境中对肿瘤转移的影响尚不清楚。在本研究中，我们旨在探讨紫草素在炎症微环境中对肿瘤转移的潜在影响及其潜在的分子机制。结果发现，在体外THP-1细胞条件培养基（THP-1- cm）模拟的炎症微环境中，紫草素显著抑制人肺腺癌细胞A549和H1299的上皮-间质转化（EMT）、迁移和侵袭。此外，我们发现THP-1-CM中表达的白细胞介素-6 （IL-6）促进肺腺癌细胞的EMT，紫草素显著抑制IL-6诱导的EMT和细胞运动。此外，紫草素还能抑制il -6诱导的信号传导和转录激活因子3 （STAT3）的磷酸化，阻止磷酸化的STAT3 （p-STAT3）转运到细胞核中，抑制p-STAT3的转激活活性。此外，我们还发现紫草素在体内抑制A549细胞的肺转移、EMT和p-STAT3的表达。此外，IL-6水平在人肺腺癌组织中与肿瘤-淋巴结-转移分期和淋巴结转移显著相关，其表达与肿瘤相关巨噬细胞（TAM）浸润相关。总之，这些结果表明，紫草素在涉及IL-6/STAT3信号通路的炎症微环境中抑制人肺腺癌细胞的迁移和侵袭。
Increasing evidence indicates that the inflammatory tumor microenvironment can lead to cancer cell metastasis. Shikonin, which is extracted from the Chinese herb Zicao (the dried root ofLithospermum erythrorhizon), possesses various pharmacological effects, but its effect on tumor metastasis in the inflammatory microenvironment remains unknown. In the present study, we aimed to investigate the potential effect of shikonin on tumor metastasis in an inflammatory microenvironment as well as the underlying molecular mechanisms. It was found that, in the inflammatory microenvironment simulated by THP-1 cell conditioned medium (THP-1-CM)in vitro, shikonin significantly inhibited the epithelial-mesenchymal transition (EMT), migration and invasion of human lung adenocarcinoma cell lines A549 and H1299. In addition, we found that interleukin-6 (IL-6), which is expressed in THP-1-CM, promoted the EMT of lung adenocarcinoma cells, and shikonin markedly inhibited IL-6-induced EMT and cell motility. Moreover, shikonin inhibited IL-6-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3), prevented phosphorylated STAT3 (p-STAT3) translocation into the nucleus, and suppressed p-STAT3 transactivation activity. Additionally, it was found that shikonin inhibited lung metastasis, EMT and expression of p-STAT3 of A549 cellsin vivo. Furthermore, IL-6 levels in human lung adenocarcinoma tissues were significantly associated with tumor-node-metastasis stage and lymph node metastasis, and its expression was correlated with tumor-associated macrophage (TAM) infiltration. Together, these results suggest that shikonin suppresses the migration and invasion of human lung adenocarcinoma cells in an inflammatory microenvironment involving the IL-6/STAT3 signaling pathway.