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
  • 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: [email protected].
  • 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: [email protected].
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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