Direct effects of the small molecule PD‑L1 inhibitor BMS‑202 on A375 melanoma cells: Anti‑tumor activity accompanied by increased mitochondrial function.

The aim of the present study was to investigate the direct effects of BMS‑202 on melanoma cells. The small molecule programmed cell death ligand 1 (PD‑L1) inhibitor BMS‑202 was used to treat A375 melanoma cells. The cell distribution of BMS‑202 was examined using low‑power and high‑resolution confocal microscopy, focusing on its localization in mitochondria. The impact of BMS‑202 on mitochondrial gene expression levels, the activity of respiratory chain complexes, and the levels of reactive oxygen species and apoptosis‑related genes, including Bax, Bcl‑2, PARP and caspase‑3, were assessed by quantitative PCR and western blotting. Additionally, tumor cell viability, proliferation, migration and invasion were evaluated in vitro, with in vivo experiments conducted through the construction of tumor‑bearing mouse models and Ki‑67 immunohistochemical staining to validate tumor proliferation. The function of mitochondria was inhibited using a pyruvate carrier inhibitor to examine how this affected the action of BMS‑202. The results revealed that BMS‑202 can inhibit tumor cell function and promote apoptosis. Furthermore, BMS‑202 was shown to enter the mitochondria where it may bind to PD‑L1 and improve mitochondrial function. By inhibiting mitochondrial function, the antitumor effects of BMS‑202 can be enhanced. Overall, the present study provides information on the potential antitumor mechanisms of BMS‑202 as well as a theoretical basis for its application in melanoma therapy.