Therapeutic Potential of Pioglitazone-Augmented Indocyanine Green-Driven Photodynamic Therapy in Papillary Thyroid Cancer: An In Vitro Study.

PURPOSE: Among thyroid malignancies, papillary thyroid carcinoma (PTC) occurs most frequently, and therapeutic resistance remains a major obstacle in advanced disease. In this study, we evaluated the potential of pioglitazone (PIO), a peroxisome proliferator-activated receptor gamma agonist, to enhance the efficacy of indocyanine green (ICG)-mediated photodynamic therapy (PDT) in B-CPAP human PTC cells. METHODS: After dose optimization, PIO and ICG were tested individually and in combination with laser irradiation (808 nm, 50 J/cm2). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test was utilized to assess cell viability, while intracellular reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were examined to better elucidate the underlying mechanisms. RESULTS: PIO alone showed minimal cytotoxicity in B-CPAP cells, whereas ICG-PDT induced a moderate reduction in viability. The combined treatment with 64.5 μM ICG and 509.0 μM PIO under PDT conditions significantly decreased cell survival to ∼50%, resulting in a substantial elevation in ROS levels and disruption of MMP. Importantly, this combination also exhibited cytotoxic effects in a non-malignant thyroid epithelial cell line (Nthy-ori 3-1), though to a lesser extent. CONCLUSIONS: These findings demonstrate that PIO potentiates the antitumor activity of ICG-PDT by inducing oxidative stress and mitochondrial dysfunction. This in vitro approach suggests a rational, combinatorial strategy that merits further investigation in preclinical models of thyroid cancer.