The COX-2 Inhibitor Celecoxib Sensitizes Nasopharyngeal Carcinoma Cells to Ferroptosis.

IF 2.3 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2025-01-06 DOI:10.2174/0115680096337720241030055036

Dawei Li, Shuang Guo, Kunrong Wang, Zhaoqi Liu, Taixin Yu, Yingqiu Zhang

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引用次数: 0

Abstract

Background: Nasopharyngeal cancer (NPC) is prevalent in Southeast Asia and North Africa, which is generally associated with limited treatment options and poor patient prognosis.

Objective: Ferroptosis is a recently observed cell death modality and has been shown to link to the efficacy of different anti-cancer treatments, thus offering opportunities to the development of novel therapies. This study aims to investigate the potentiating effects of COX-2 inhibitors on ferroptosis in nasopharyngeal cancer.

Methods: The inhibitory effects of COX-2 inhibitors celecoxib and rofecoxib on nasopharyngeal cancer cells were assessed with MTT, colony formation, sphere formation, Transwell, wound healing assays. The status of COX-2 with celecoxib and rofecoxib treatment was investigated by Western blotting and immunofluorescence experiments. Ferroptosis was induced with the GPX4 inhibitor RSL3 with or without COX-2 inhibition and was monitored by fluorescence microscopy. Transcriptomic profiling was conducted with 5-8F cells treated with DMSO as control or celecoxib, and ferroptosis-related candidates were validated by RT- PCR analysis.

Results: Celecoxib and rofecoxib effectively inhibited the growth and migration of nasopharyngeal cancer cells. Both inhibitors evidently sensitized nasopharyngeal cancer cells to ferroptosis induction by RSL3, with celecoxib outperforming rofecoxib. Celecoxib treatment resulted in significantly differentially expressed genes in 5-8F cells, among which CHAC1 was validated as a ferroptosis-related target.

Conclusion: The COX-2 inhibitor celecoxib effectively sensitized nasopharyngeal cancer cells to ferroptosis induction.

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COX-2抑制剂塞来昔布使鼻咽癌细胞对铁下垂致敏。

背景：鼻咽癌（NPC）在东南亚和北非流行，通常与治疗选择有限和患者预后差有关。目的：铁下垂是最近观察到的一种细胞死亡方式，已被证明与不同抗癌治疗的疗效有关，从而为开发新的治疗方法提供了机会。本研究旨在探讨COX-2抑制剂对鼻咽癌铁下垂的增强作用。方法：采用MTT法、菌落形成法、球形成法、Transwell法、创面愈合法评价COX-2抑制剂塞来昔布和罗非昔布对鼻咽癌细胞的抑制作用。采用Western blotting和免疫荧光实验观察COX-2在塞来昔布和罗非昔布治疗后的状态。用GPX4抑制剂RSL3诱导铁下垂，有或没有COX-2抑制，并通过荧光显微镜监测。以DMSO作为对照或塞来昔布处理的5-8F细胞进行转录组学分析，并通过RT- PCR分析验证与铁凋亡相关的候选细胞。结果：塞来昔布和罗非昔布能有效抑制鼻咽癌细胞的生长和迁移。两种抑制剂对RSL3诱导的鼻咽癌细胞均有明显的致敏作用，其中塞来昔布优于罗非昔布。塞来昔布治疗导致5-8F细胞中基因表达显著差异，其中CHAC1被证实是铁致凋亡相关的靶点。结论：COX-2抑制剂塞来昔布对诱导鼻咽癌细胞铁下垂具有有效的致敏作用。

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

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

期刊介绍： Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.