2. Academic Validation
  3. Ferroptosis promotes 5-aminolevulinate acid-based photodynamic therapy in cervical cancer

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

  • Photodiagnosis Photodyn Ther. 2025 Aug:54:104726. doi: 10.1016/j.pdpdt.2025.104726.
Qiyu Liu 1,  Qin Han 1,  Jiaxin Shi 1,  Zhangxin Wu 1,  Lingyu Ma 1,  Yuan Li 1,  Haojie He 2,  Hongyan Guo 3
Affiliations

Affiliations

  • 1 Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, PR China.
  • 2 Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, PR China. Electronic address: haojiehe@yahoo.com.
  • 3 Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, PR China; National Clinical Research Center for Obstetrics and Gynecology (Peking University Third Hospital), Beijing 100191, PR China; Key Laboratory of Assisted Reproduction (Peking University), Ministry of Education, Beijing 100191, PR China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing 100191, PR China. Electronic address: 9163168430@bjmu.edu.cn.
PMID: 40680910 DOI: 10.1016/j.pdpdt.2025.104726
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.

Keywords

5-aminolevulinate acid; Cervical cancer; Ferroptosis; Photodynamic therapy.

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