Cordycepin Potentiates Photodynamic Therapy Efficacy in Esophageal Cancer Cells via Modulation of the PI3K/AKT/FOXO3 signaling pathway

Photodynamic therapy (PDT) has been approved for the treatment of esophageal cancer (EC), but its effectiveness remains limited. Emerging evidence suggests that cordycepin can synergize with other therapeutic modalities. Therefore, we investigated whether the combination of PDT and cordycepin could enhance the therapeutic efficacy. Using colony formation assay and flow cytometry, we assessed the effects of the viability and apoptosis on EC cells. RT-qPCR and Western blot analyses were employed to examine the expression of pathway-related proteins and genes. In vitro, results demonstrated that the combination of PDT and cordycepin enhanced apoptosis to inhibit cell growth and increased the production of immune factors IL-18 and IL-1β. Furthermore, it inhibited the expression levels of p-PI3K/PI3K, p-AKT/AKT, and Bcl-2, while enhancing the expression levels of FOXO3, Caspase-3, Bax, Caspase-9, and Cyt-C. In conclusion, PDT combined with cordycepin enhances the anti-cancer effect through the PI3K/AKT/FOXO3 signaling pathway in EC cells. The experiment provides a theoretical basis for the combination of PDT and cordycepin to become a new strategy which may increase the efficacy of PDT in esophageal cancer.