@article{Li2026, 
author = {Ju Li and Pengcheng Rao and Dan Yang and Tong Zhou and Jianguo Gan and Die Lv and Shuting Zhou and Yang Peng and Xiaoqiang Xia and Qianming Chen and Yuchen Jiang and Jian Jiang and Xiaoping Xu and Xiaodong Feng},
title = {Synergistic Cell Death: Cisplatin Inflames Tumors by Coordinating Multiple Death Programs},
year = {2026},
journal = {BIOCELL},
volume = {50},
number = {5},
keywords = {Cisplatin, programmed cell death, pyroptosis, necroptosis, ferroptosis, apoptosis},
url = {https://www.sciopen.com/article/10.32604/biocell.2026.075437},
doi = {10.32604/biocell.2026.075437},
abstract = {ObjectiveMultiple programmed cell death (PCD) pathways have been individually reported to be triggered by cisplatin, but whether and how they are co-regulated remains unclear. In this study, we comprehensively investigate the spectrum of cisplatin-induced PCD.MethodsWe employed integrated in vitro and in vivo models, including human cancer cell lines, a Cal27 xenograft mouse model, and paired clinical specimens from an oral squamous cell carcinoma patient receiving neoadjuvant cisplatin-based chemotherapy. A comprehensive methodological suite-encompassing cell death assays, Western blotting, Hematoxylin and eosin staining, immunofluorescence, Cyclic multiplexed tissue staining, and pathway-specific pharmacological inhibitors was utilized to dissect the activation of apoptosis, necroptosis, pyroptosis, and ferroptosis.ResultsCisplatin simultaneously upregulates markers of PCD pathways (including apoptosis, necroptosis, pyroptosis, and ferroptosis) in a dose- or time-dependent manner. Pharmacological inhibition or genetic knockdown of key genes in each pathway significantly reduced cytotoxicity, confirming their functional roles. Notably, indicators of key pro-inflammatory death modalities, pyroptosis and ferroptosis, were prominently co-upregulated in both xenograft tumors and clinical patient samples, suggesting that these two forms of PCD may represent the predominant death forms in cisplatin-induced tumor cell death.ConclusionCisplatin induces the coordinated activation of multiple cell death programs within a unified framework. Prominent engagement of immunogenic cell death pathways, particularly pyroptosis and ferroptosis, provides a mechanistic basis for the clinically observed synergy between cisplatin and immune checkpoint blockade therapy.}
}