Near-infrared-activated indocyanine green enhances cisplatin-induced c-Fos-mediated apoptosis in colorectal cancer cells

Colorectal cancer (CRC) treatment remains limited by chemoresistance, highlighting the need for combination strategies that enhance therapeutic responses. Indocyanine green (ICG) is a clinically approved near-infrared (NIR)-responsive agent with photothermal and photodynamic properties. Here, we investigated the effects of NIR-activated ICG combined with cisplatin (CDDP) and the associated apoptotic mechanisms in HCT116 and HT29 CRC cells. NIR-activated ICG enhanced CDDP-induced cytotoxicity, with HCT116 cells exhibiting greater sensitivity than the more CDDP-resistant HT29 cells. Comparable intracellular ICG accumulation between the cell lines indicated that differential sensitivity was unlikely to result from differences in ICG uptake. RT-qPCR revealed preferential FOS induction in HCT116 cells, which was confirmed at the c-Fos protein level. Consistently, Annexin V/PI and cell-cycle analyses demonstrated greater apoptosis and sub-G1 accumulation in HCT116 cells. Combination treatment was further associated with reduced Bcl-2 and FBXL10 expression and increased caspase-3 and PARP cleavage. Collectively, these findings demonstrate that NIR-activated ICG potentiates CDDP-induced apoptosis and identify c-Fos-associated apoptotic signaling as a potential molecular determinant of treatment responsiveness in CRC cells.