芹菜素通过调节TNF-α/NF-κB信号和AIM2炎症小体激活缓解肺腺癌细胞焦亡
Apigenin Alleviates Pyroptosis in Lung Adenocarcinoma Cells by Modulating TNF-α/NF-κB Signaling and AIM2 Inflammasome Activation.
作者
作者单位
- Department of Thoracic Surgery, Yantaishan Hospital Affiliated to Shandong Medical and Pharmaceutical University, Yantai, Shandong, China.
- Department of Biochemistry and Molecular Biology, Shandong Medical and Pharmaceutical University, Yantai, Shandong, China.
- Department of Clinical Laboratory, The Second Medical College of Shandong Medical and Pharmaceutical University, Yantai, Shandong, China.
- Department of Oncology, Yantaishan Hospital Affiliated to Shandong Medical and Pharmaceutical University, Yantai, Shandong, China.
摘要
中文
焦亡相关信号有助于肺腺癌（LUAD）的进展和预后。芹菜素（AP）具有抗炎和细胞保护特性，但其对受损LUAD细胞中焦亡相关信号的影响仍不清楚。用羰基氰化物间氯苯腙（CCCP）和硫酸亚铁（FeSO4）处理A549细胞以建立细胞损伤模型。在AP处理后评估细胞形态、Cell Counting Kit-8信号和焦亡相关蛋白。使用网络药理学、分子对接、分子动力学模拟以及癌症基因组图谱和基因表达综合数据库的分析来排序候选靶点、表征焦亡相关基因并开发预后特征。CCCP/FeSO4降低CCK-8信号并诱导形态损伤，而AP部分逆转了这些变化。AP还减少了GSDMD-N、caspase-1、IL-1β、TNF-α/NF-κB通路蛋白、AIM2和ASC的改变。TNF被优先列为候选靶点，计算分析预测了潜在的稳定AP-TNF相互作用，但未显示直接结合。生物信息学分析确定了不同的焦亡相关LUAD亚组，并生成了一个预后特征，在训练和外部验证队列中对生存进行了分层。AIM2还被优先列为LUAD和应激相关候选。AP减弱了CCCP/FeSO4诱导的A549细胞损伤和焦亡相关的分子变化，可能通过TNF-α/NF-κB和AIM2相关信号。需要进一步的机制验证。
English
Pyroptosis-related signaling contributes to lung adenocarcinoma (LUAD) progression and prognosis. Apigenin (AP) has anti-inflammatory and cytoprotective properties, but its effects on pyroptosis-associated signaling in injured LUAD cells remain unclear. A549 cells were treated with carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and ferrous sulfate (FeSO4) to establish a cellular injury model. Cell morphology, Cell Counting Kit-8 signals, and pyroptosis-associated proteins were assessed after AP treatment. Network pharmacology, molecular docking, molecular dynamics simulations, and analyses of The Cancer Genome Atlas and Gene Expression Omnibus datasets were used to prioritize candidate targets, characterize pyroptosis-related genes, and develop a prognostic signature. CCCP/FeSO4 reduced CCK-8 signals and induced morphological injury, whereas AP partially reversed these changes. AP also reduced alterations in GSDMD-N, caspase-1, IL-1β, TNF-α/NF-κB pathway proteins, AIM2, and ASC. TNF was prioritized as a candidate target, and computational analyses predicted a potentially stable AP-TNF interaction without demonstrating direct binding. Bioinformatic analyses identified distinct pyroptosis-related LUAD subgroups and generated a prognostic signature that stratified survival in training and external validation cohorts. AIM2 was additionally prioritized as a LUAD- and stress-associated candidate. AP attenuated CCCP/FeSO4-induced injury and pyroptosis-associated molecular changes in A549 cells, potentially through TNF-α/NF-κB and AIM2-related signaling. Further mechanistic validation is required.
分类与指标
- 研究类型
- 基础研究
- 病种
- 肺癌
- JCR 分区
- Q2
- 影响因子
- 2.6
- 新锐分区
- 4区