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

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

  • Mol Med Rep. 2025 Sep;32(3):242. doi: 10.3892/mmr.2025.13607.
Nieng Zhang # 1,  Fenglan Feng # 2,  Ruonan Dang 3,  Xiaoqing Zhao 4,  Xingrong Wang 1,  Yuqi Yang 4,  Jinjin Deng 5,  Yujie Wang 1,  Zhuofan Wen 1,  Wei Meng 5,  Xinglan Huang 6,  Shunying Zhang 7,  Yuqiong Deng 8,  Caifeng Huang 1,  Peng Yan 9,  Zhongrong Liu 1,  Xiping Cheng 1
Affiliations

Affiliations

  • 1 Department of Dermatology, The First Affiliated Hospital of Guangzhou Medical University, School of First Clinical Medicine, Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China.
  • 2 The Key Laboratory of Advanced Interdisciplinary Studies, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China.
  • 3 Department of Chinese Medicine, The First Affiliated Hospital of Guangzhou Medical University, School of First Clinical Medicine, Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China.
  • 4 Department of Traditional Chinese Medicine, Institute of Integrated Chinese and Western Medicine of Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China.
  • 5 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China.
  • 6 Department of Dermatology, Guangzhou Twelfth People's Hospital, Guangzhou, Guangdong 510620, P.R China.
  • 7 Department of Dermatology, Songshan Lake Central Hospital of Dongguan City of Southern Medical University, Dongguan, Guangdong 523000, P.R. China.
  • 8 Department of Dermatology, Panyu Maternal and Child Care Service Centre of Guangzhou, Guangzhou, Guangdong 511400, P.R. China.
  • 9 Department of Critical Care Medicine, Guangzhou First People's Hospital, South China University of Technology, Guangzhou, Guangdong 510180, P.R. China.
  • # Contributed equally.
PMID: 40641134 DOI: 10.3892/mmr.2025.13607
Abstract

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.

Keywords

melanoma; mitochondria; programmed cell death ligand 1 inhibitor.

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