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

IF 2.5 3区医学 Q3 ONCOLOGY

World Journal of Surgical Oncology Pub Date : 2025-03-01 DOI:10.1186/s12957-025-03692-7

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

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引用次数: 0

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.

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背景：顺铂（DDP）是一种常用的化疗药物。然而，在非小细胞肺癌（NSCLC）患者中，DDP耐药性的产生大大降低了以DDP为基础的化疗的效果。本研究探讨了内皮素1（EDN1）对非小细胞肺癌患者DDP耐药性的影响：方法：采用细胞计数试剂盒-8和Transwell迁移与侵袭试验检测NSCLC细胞的增殖、侵袭和迁移。用 ELISA 分析炎症细胞因子的浓度。通过 Western 印迹分析了肿瘤坏死因子（TNF）信号通路的相关蛋白水平。此外，还建立了异种移植肿瘤小鼠模型，以探讨 EDN1 在体内的作用：结果表明，DDP抗性上调了EDN1在NSCLC细胞中的表达、细胞活力、侵袭、迁移和炎症反应，而抑制EDN1后结果逆转。EDN1通过调节TNF信号通路影响NSCLC对DDP的耐受性。过表达 TNF 受体-1（TNFR1）可逆转沉默 EDN1 引起的 A549/DDP 细胞活力、侵袭、迁移和炎症的降低。此外，沉默 EDN1 还可抑制肿瘤生长以及 EDN1 和 TNFR1 的蛋白水平：结论：EDN1通过调节TNF信号通路促进了NSCLC细胞对DDP的耐药性，为NSCLC提供了一种潜在的治疗干预策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

World Journal of Surgical Oncology ONCOLOGY-SURGERY

CiteScore

4.70

自引率

15.60%

发文量

362

审稿时长

3 months

期刊介绍： World Journal of Surgical Oncology publishes articles related to surgical oncology and its allied subjects, such as epidemiology, cancer research, biomarkers, prevention, pathology, radiology, cancer treatment, clinical trials, multimodality treatment and molecular biology. Emphasis is placed on original research articles. The journal also publishes significant clinical case reports, as well as balanced and timely reviews on selected topics. Oncology is a multidisciplinary super-speciality of which surgical oncology forms an integral component, especially with solid tumors. Surgical oncologists around the world are involved in research extending from detecting the mechanisms underlying the causation of cancer, to its treatment and prevention. The role of a surgical oncologist extends across the whole continuum of care. With continued developments in diagnosis and treatment, the role of a surgical oncologist is ever-changing. Hence, World Journal of Surgical Oncology aims to keep readers abreast with latest developments that will ultimately influence the work of surgical oncologists.