Cordycepin Combined with Photodynamic Therapy Induces Pyroptosis in Breast Cancer Cells via the ROS/NLRP3/Caspase-1/GSDMD Signaling Pathway.

OBJECTIVE: This study aimed to investigate the molecular mechanism by which cordycepin (Cor) combined with photodynamic therapy (PDT) exerts cytotoxicity against human breast cancer cells in vitro. METHODS: CCK‑8 assay, colony formation assay and Calcein‑AM/PI staining were used to evaluate cell proliferation. DCFH‑DA and JC‑1 staining combined with flow cytometry were performed to detect intracellular ROS and mitochondrial membrane potential. LDH release assay, ELISA and western blot were adopted to assess cell damage, inflammatory cytokine secretion and pyroptosis‑related protein expression. RESULTS: Combined Cor and PDT treatment produced robust anti‑tumour effects and oxidative stress accumulation in breast cancer cell lines. This combinatorial regimen modulated the expression of core pyroptotic molecules and stimulated the secretion of pro‑inflammatory mediators. Pharmacological inhibition of ROS or caspase‑1 attenuated the anti‑tumour effects induced by combined treatment. CONCLUSIONS: Cor synergistically enhances the anti-proliferative effect of PDT on breast cancer cells. This combinatorial treatment induces GSDMD-dependent pyroptosis via caspase-1 activation. Our findings offer new experimental evidence and research insights for the potential use of active components from traditional Chinese medicine in tumor therapy.