Key Laboratory of Environment Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing, China.
Environ Toxicol. 2023 May;38(5):1090-1099. doi: 10.1002/tox.23750. Epub 2023 Feb 1.
Previous studies have shown the role of bacterial lipopolysaccharide (LPS) in promoting tumor progression. Our previous study found that the community richness of LPS-producing bacteria was significantly increased in the fresh stool samples of esophageal cancer (EC) patients, but the relative LPS levels and underlying mechanism in EC progression remain unknown. In this study, an case-control study found that the content of LPS was higher in serum of EC patients. Functional experiments of CCK8 assay and transwell assay showed that LPS contributed to the proliferation, migration, invasion of EC109 cells. Meanwhile, LPS induced EC109 to secrete IL-6 and TGF-β1. Western blot analysis revealed the level of TLR4 and NF-κB increased significantly after LPS treatment. Epithelial marker E-cadherin was significantly down-regulated and interstitial marker N-cadherin and Vimentin were up-regulated after LPS treatment. However, TAK242 (TLR4 inhibitor) or PDTC (NF-κB inhibitor) could eliminate the inflammatory and EMT-promoting effects of LPS. In total, our results suggested that LPS exacerbated to the migration, invasion, and epithelial-mesenchymal transition of EC109 cells by TLR4/NF-κB axis. High level LPS may have a critical effect on the occurrence and development of EC.
先前的研究表明细菌脂多糖（LPS）在促进肿瘤进展中起作用。我们之前的研究发现，食管癌（EC）患者新鲜粪便样本中 LPS 产生菌的群落丰富度显著增加，但在 EC 进展中相对 LPS 水平及其潜在机制仍不清楚。在这项研究中，一项病例对照研究发现 EC 患者血清中的 LPS 含量更高。CCK8 检测和 Transwell 检测的功能实验表明，LPS 有助于 EC109 细胞的增殖、迁移和侵袭。同时，LPS 诱导 EC109 分泌 IL-6 和 TGF-β1。Western blot 分析显示，LPS 处理后 TLR4 和 NF-κB 的水平显著增加。LPS 处理后上皮标志物 E-钙黏蛋白明显下调，间质标志物 N-钙黏蛋白和波形蛋白上调。然而，TAK242（TLR4 抑制剂）或 PDTC（NF-κB 抑制剂）可以消除 LPS 的炎症和 EMT 促进作用。总之，我们的结果表明，LPS 通过 TLR4/NF-κB 轴加剧了 EC109 细胞的迁移、侵袭和上皮-间充质转化。高水平 LPS 可能对 EC 的发生和发展有重要影响。
