肺癌是近年来发病率最高的癌症之一，主要由非小细胞肺癌、小细胞肺癌和神经内分泌肿瘤三种疾病组成。这种恶性肿瘤的发病率和死亡率在全球男性和女性人口中最高。在我国，肺癌已成为最常见的癌症疾病和导致癌症死亡的主要原因，因此寻找肺癌治疗靶点非常重要。基于以前的研究，我们推测TLR4-Myd88-NFκB信号通路可能参与了hmgb1诱导的A549细胞中的EMT，并且daphnetin也可以通过TLR4-Myd88-NFκB途径抑制hmgb1诱导的EMT，但相关研究尚未将其与hmgb1诱导的EMT联系起来。因此，本研究的创新性在于测试这两个假设并分析daphnetin如何影响A549细胞中hmgb1诱导的上皮-间质转化（EMT）机制，旨在为肺腺癌细胞的临床治疗奠定基础。在HMGB1+TLR4-shRNA组和HMGB1+daphnetin组中，增殖率和迁移细胞数相对于HMGB1组明显下降（P＜0.0001）。相对于HMGB1组，HMGB1+TLR4-shRNA组和HMGB1+daphnetin组的细胞内TLR4、Myd88、NFκB、vimentin和snail1蛋白表达显著下降（P＜0.001），而E-cadherin的表达明显增加（P＜0.001）。TLR4-MyD88-NFκB通路与A549细胞中HMGB1诱导的EMT相关。Daphnetin通过TLR4-Myd88-NFκB途径对A549细胞中HMGB1诱导的EMT有抑制作用。

As a cancer with the highest incidence in recent years, lung cancer is mainly composed of three diseases: non-small cell lung cancer, small cell lung cancer and neuroendocrine tumor. The morbidity and mortality of this malignant tumor are the highest in both male and female populations worldwide. In my country, lung cancer has become the most common cancer disease and the leading cause of cancer death, so it is extremely important to find lung cancer therapeutic targets. Based on previous studies, we speculated that the TLR4-Myd88-NFκB pathway may be involved in hmgb1-induced EMT in A549 cells, and daphnetin may also inhibit hmgb1-induced EMT through the TLR4-Myd88-NFκB pathway in A549 cells, but related studies have not linked it to hmgb1-induced EMT. Therefore, the innovation of this study is to test these two conjectures and analyze how daphnetin affects the epithelial-mesenchymal transition (EMT) mechanism induced by HMGB1 in human lung adenocarcinoma cells (A549 cell line), aiming at lung adenocarcinoma cells, foundation for clinical treatment. The proliferation rate and the migrating cell number presented an obvious decrease in the HMGB1+TLR4-shRNA group and the HMGB1+daphnetin group relative to the HMGB1 group (P < 0.0001). The intracellular expression of TLR4, Myd88, NFκB, vimentin and snail1 proteins were significantly decreased (P < 0.001), while that of E-cadherin presented a remarkable increase (P < 0.001) in the HMGB1+TLR4-shRNA and HMGB1+daphnetin group compared with the HMGB1 group. TLR4-MyD88-NFκB pathway is associated with HMGB1-induced EMT in A549 cells. Daphnetin had an inhibitory effect on HMGB1-induced EMT via the TLR4-Myd88-NF-κB pathway in A549 cells.