Photodynamic therapy modulates proliferation in carcinoma and melanoma: from clonogenic survival to tumor development

Abstract Cutaneous carcinomas and melanoma are important skin malignancies for which photodynamic therapy (PDT) has shown therapeutic potential. Although the biological effects of PDT have been extensively investigated, particularly in carcinomas, the phenotype and behavior of tumor cells that survive treatment remain poorly understood, despite their potential role in tumor persistence and recurrence. Characterizing the proliferative behavior of PDT-surviving tumor cells may therefore provide insights into the cellular consequences of treatment and their potential implications for tumor regrowth. In this study, we investigated the proliferative capacity of cutaneous squamous cell carcinoma and melanoma cells following porphyrin-mediated PDT using a combined in vitro clonogenic assay and in vivo tumor model of treated cells. Temporal recovery was assessed using viability and clonogenic assays at two lethal doses of PDT (LD₅₀ and LD₃₀). The results demonstrated that the temporal impact of PDT on proliferative capacity was dose-dependent, persisting for up to 72 h in the LD₅₀ group. Tumors derived from LD₅₀-treated cells showed reduced volume, delayed onset, and slower growth, corroborated by decreased proliferating cell nuclear antigen (PCNA) expression. These findings support PDT as a strategy for melanoma and define a critical “damage window,” during which adjuvant therapies may improve efficacy and limit recurrence.