Nanchang University, Nan Chang city, China.
Department of Clinical Laboratory, The Fourth Affiliated Hospital of Nanchang University, Nan Chang city, China.
Biotechnol Genet Eng Rev. 2024 Nov;40(3):1489-1510. doi: 10.1080/02648725.2023.2194092. Epub 2023 Mar 30.
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 ( < 0.0001). The intracellular expression of TLR4, Myd88, NFκB, vimentin and snail1 proteins were significantly decreased ( < 0.001), while that of E-cadherin presented a remarkable increase ( < 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.
作为近年来发病率最高的癌症，肺癌主要由三种疾病组成：非小细胞肺癌、小细胞肺癌和神经内分泌肿瘤。这种恶性肿瘤在全球男性和女性中的发病率和死亡率都最高。在我国，肺癌已成为最常见的癌症疾病和癌症死亡的主要原因，因此寻找肺癌治疗靶点极为重要。基于以往的研究，我们推测 TLR4-Myd88-NFκB 通路可能参与 hmgb1 诱导的 A549 细胞 EMT，并且瑞香素也可能通过 TLR4-Myd88-NFκB 通路抑制 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，本研究的创新之处在于验证这两个假设，并分析瑞香素如何影响人肺腺癌细胞（A549 细胞系）中 hmgb1 诱导的上皮-间充质转化（EMT）机制，旨在为肺腺癌细胞，为临床治疗提供基础。HMGB1+TLR4-shRNA 组和 HMGB1+瑞香素组的细胞增殖率和迁移细胞数明显低于 HMGB1 组（ < 0.0001）。HMGB1+TLR4-shRNA 组和 HMGB1+瑞香素组细胞内 TLR4、Myd88、NFκB、波形蛋白和 snail1 蛋白的表达明显降低（ < 0.001），而 E-钙黏蛋白的表达明显升高（ < 0.001）与 HMGB1 组相比。TLR4-MyD88-NFκB 通路与 A549 细胞中 HMGB1 诱导的 EMT 有关。瑞香素通过 TLR4-Myd88-NF-κB 通路对 A549 细胞中 HMGB1 诱导的 EMT 具有抑制作用。
