Ferroptosis promotes 5-aminolevulinate acid-based photodynamic therapy in cervical cancer

IF 2.6 3区医学 Q2 ONCOLOGY

Photodiagnosis and Photodynamic Therapy Pub Date : 2025-07-16 DOI:10.1016/j.pdpdt.2025.104726

Qiyu Liu , Qin Han , Jiaxin Shi , Zhangxin Wu , Lingyu Ma , Yuan Li , Haojie He , Hongyan Guo

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引用次数: 0

Abstract

Background

Cervical cancer has the highest incidence rate among all gynecologic malignancies. Photodynamic therapy (PDT) is a minimal invasive treatment widely used in various tumors. Intracellular generation of reactive oxygen species (ROS) is the essential effect in PDT, which also plays a pivotal role in ferroptosis. We hypothesize that ferroptosis inducer could enhance 5-Aminolevulinic acid (5-ALA) based PDT in cervical cancer.

Methods

In vitro efficacy of 5-ALA-based photodynamic therapy was assessed via viability and apoptosis of cervical cancer cell line SiHa. Ferroptosis related markers were detected in SiHa cells received 5-ALA-PDT treatment. Anti-tumor effects of ferroptosis inducer sorafenib on 5-ALA-based photodynamic therapy were evaluated in both cell line and mouse model.

Results

Efficacy of 5-ALA-based photodynamic therapy was validated in SiHa cervical cancer cells. Increased intracellular generation of ROS and lipid ROS, accompanied by decreased GPX4 expression was observed after 5-ALA-PDT treatment, indicating ferroptosis triggered by photodynamic therapy. Ferroptosis inducer sorafenib, a clinical approved cancer drug, promotes 5-ALA-based photodynamic therapy in SiHa cells. In vivo combined anti-tumor effect of sorafenib and 5-ALA-based photodynamic therapy was confirmed in cervical cancer xenografts.

Conclusion

We identified that 5-ALA-PDT inhibited cell viability and induced ferroptosis in cervical cancer. Ferroptosis inducer sorafenib promotes 5-ALA-based photodynamic therapy. These findings may provide new insights into mechanisms of photodynamic therapy and cervical cancer treatment in the future.

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下垂铁促进5-氨基乙酰酸为基础的光动力治疗宫颈癌。

背景：宫颈癌在所有妇科恶性肿瘤中发病率最高。光动力治疗（PDT）是一种广泛应用于各种肿瘤的微创治疗方法。细胞内活性氧（ROS）的产生是PDT的重要作用，在铁下垂中也起着关键作用。我们假设铁下垂诱导剂可以增强5-氨基乙酰丙酸（5-ALA）在宫颈癌中的PDT。方法：通过对宫颈癌细胞株SiHa细胞活力和凋亡情况的观察，评价5- ala光动力疗法的体外疗效。在5-ALA-PDT处理的SiHa细胞中检测到铁下垂相关标志物。在细胞系和小鼠模型上评价了铁下垂诱导剂索拉非尼对5- ala光动力治疗的抗肿瘤作用。结果：基于5- ala的光动力疗法对SiHa宫颈癌细胞的治疗效果得到验证。5-ALA-PDT治疗后，细胞内ROS和脂质ROS生成增加，GPX4表达下降，提示光动力治疗引发铁下垂。铁下垂诱导剂索拉非尼是一种临床批准的抗癌药物，可促进SiHa细胞中基于5- ala的光动力治疗。索拉非尼联合5- ala光动力治疗宫颈癌异种移植物的体内抗肿瘤效果得到证实。结论：5-ALA-PDT抑制宫颈癌细胞活力，诱导铁下垂。铁下垂诱导剂索拉非尼促进5- ala光动力治疗。这些发现可能为今后光动力治疗和宫颈癌治疗的机制提供新的见解。

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

Photodiagnosis and Photodynamic Therapy ONCOLOGY-

CiteScore

5.80

自引率

24.20%

发文量

509

审稿时长

50 days

期刊介绍： Photodiagnosis and Photodynamic Therapy is an international journal for the dissemination of scientific knowledge and clinical developments of Photodiagnosis and Photodynamic Therapy in all medical specialties. The journal publishes original articles, review articles, case presentations, "how-to-do-it" articles, Letters to the Editor, short communications and relevant images with short descriptions. All submitted material is subject to a strict peer-review process.