ICG-PDT Attenuates TGF-β1-Induced EMT-Associated Phenotypes and Modulates Autophagy-Related Processes in OSCC Cells

(1) Background: Epithelial–mesenchymal transition (EMT) facilitates tumor cell migration and invasion. Autophagy contributes to tumor cell survival by maintaining metabolic homeostasis. This study aimed to investigate how indocyanine green-mediated photodynamic therapy (ICG–PDT) affects these two important processes in oral squamous cell carcinoma (OSCC). (2) Methods: Transforming growth factor-β1 (TGF-β1) was used to induce EMT. The effects of ICG–PDT on the EMT-associated phenotypes were evaluated using functional assays. Reactive oxygen species (ROS) generation, autophagic processes, and signaling pathways were analyzed using fluorescence staining, Western blotting, and pharmacological modulation. (3) Results: ICG-PDT attenuated TGF-β1-induced EMT-associated phenotypes. ICG–PDT induced ROS generation and caused LC3B-II and p62 accumulation, indicating modulation of the autophagic process. Pharmacological modulation of autophagy confirmed that modulation of the autophagic process may contribute to EMT inhibition. ICG–PDT can also influence the Akt/β-catenin pathway. (4) Conclusions: ICG-PDT attenuates TGF-β1-induced EMT-associated phenotypes while modulating autophagy-related processes in OSCC cells. This study provides preliminary evidence on the relationship between PDT and EMT, suggesting that targeting autophagic pathways may contribute to improving the efficacy of PDT in tumor progression.