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

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.