内皮素-1通过调节肿瘤坏死因子信号通路促进非小细胞肺癌细胞对顺铂的耐药性。

EDN1 facilitates cisplatin resistance of non-small cell lung cancer cells by regulating the TNF signaling pathway.

作者信息

Zhen Jie, Sun Long, Ji Li, Zhou Shaochong, Cui Yijin, Li Zhenwei

机构信息

Department of Thoracic Surgery, Qidong People's Hospital, Qidong Liver Cancer Institute, Affiliated Qidong Hospital of Nantong University, Qidong, China.

Department of Pathology, Qidong People's Hospital, Qidong Liver Cancer Institute, Affiliated Qidong Hospital of Nantong University, Qidong, China.

出版信息

World J Surg Oncol. 2025 Mar 1;23(1):71. doi: 10.1186/s12957-025-03692-7.

DOI:10.1186/s12957-025-03692-7

PMID:40025550

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11871734/

Abstract

BACKGROUND

Cisplatin (DDP) is a commonly utilized chemotherapeutic agent. Nevertheless, the development of resistance to DDP significantly diminishes the effectiveness of DDP-based chemotherapy in patients with non-small cell lung cancer (NSCLC). In this study, we investigated the impact of endothelin 1 (EDN1) on the resistance to DDP in NSCLC.

METHODS

The proliferation, invasion, and migration of NSCLC cells were detected by cell counting kit-8 and Transwell migration and invasion assays. ELISA was performed to analyze the inflammatory cytokines concentrations. The related protein levels of tumor necrosis factor (TNF) signaling pathway were analyzed by Western blot. Besides, a xenograft tumor mice model was established to explore the role of EDN1 in vivo.

RESULTS

The results showed that DDP-resistance upregulated EDN1 expression, cell viability, invasion, migration, and inflammation in NSCLC cells, while the results were reversed after EDN1 inhibition. EDN1 affected DDP-resistance of NSCLC by regulating TNF signaling pathway. Overexpression of TNF receptor-1 (TNFR1) reversed the decreased cell viability, invasion, migration, and inflammation induced by silencing EDN1 in A549/DDP cells. Moreover, silencing EDN1 inhibited tumor growth and the protein levels of EDN1 and TNFR1.

CONCLUSION

EDN1 promoted DDP resistance in NSCLC cells through the modulation of the TNF signaling pathway, suggesting a potential therapeutic intervention strategy for NSCLC.

摘要

背景

顺铂（DDP）是一种常用的化疗药物。然而，对DDP产生耐药性会显著降低基于DDP的化疗对非小细胞肺癌（NSCLC）患者的疗效。在本研究中，我们调查了内皮素1（EDN1）对NSCLC中DDP耐药性的影响。

方法

通过细胞计数试剂盒-8以及Transwell迁移和侵袭试验检测NSCLC细胞的增殖、侵袭和迁移能力。采用酶联免疫吸附测定（ELISA）分析炎性细胞因子浓度。通过蛋白质印迹法分析肿瘤坏死因子（TNF）信号通路的相关蛋白水平。此外，建立异种移植瘤小鼠模型以探究EDN1在体内的作用。

结果

结果显示，DDP耐药性上调了NSCLC细胞中EDN1的表达、细胞活力、侵袭、迁移和炎症，而在抑制EDN1后这些结果发生了逆转。EDN1通过调节TNF信号通路影响NSCLC的DDP耐药性。肿瘤坏死因子受体-1（TNFR1）的过表达逆转了A549/DDP细胞中因沉默EDN1而导致的细胞活力、侵袭、迁移和炎症的降低。此外，沉默EDN1可抑制肿瘤生长以及EDN1和TNFR1的蛋白水平。