免疫原性
DNA损伤
癌症研究
细胞凋亡
A549电池
癌细胞
肿瘤微环境
癌症
肺癌
免疫疗法
免疫系统
彗星试验
化学
生物
免疫学
医学
病理
DNA
生物化学
遗传学
作者
Ning Han,Ziyi Yang,Zhong-Xiong Xie,Hua‐Zhen Xu,Tingting Yu,Qi‐Rui Li,Liu‐Gen Li,Xing‐Chun Peng,Xiaoxin Yang,Jun Hu,Xiang Xu,Xiao Chen,Meifang Wang,Tong‐Fei Li
出处
期刊:Phytomedicine
[Elsevier]
日期:2023-04-01
卷期号:112: 154682-154682
被引量:31
标识
DOI:10.1016/j.phymed.2023.154682
摘要
The immunosuppressive microenvironment of lung cancer serves as an important endogenous contributor to treatment failure. The present study aimed to demonstrate the promotive effect of DHA on immunogenic cell death (ICD) in lung cancer as well as the mechanism.The lewis lung cancer cells (LLC), A549 cells and LLC-bearing mice were applied as the lung cancer model. The apoptosis, ferroptosis assay, western blotting, immunofluorescent staining, qPCR, comet assay, flow cytometry, confocal microscopy, transmission electron microscopy and immunohistochemistry were conducted to analyze the functions and the underlying mechanism.An increased apoptosis rate and immunogenicity were detected in DHA-treated LLC and tumor grafts. Further findings showed DHA caused lipid peroxide (LPO) accumulation, thereby initiating ferroptosis. DHA stimulated cellular endoplasmic reticulum (ER) stress and DNA damage simultaneously. However, the ER stress and DNA damage induced by DHA could be abolished by ferroptosis inhibitors, whose immunogenicity enhancement was synchronously attenuated. In contrast, the addition of exogenous iron ions further improved the immunogenicity induced by DHA accompanied by enhanced ER stress and DNA damage. The enhanced immunogenicity could be abated by ER stress and DNA damage inhibitors as well. Finally, DHA activated immunocytes and exhibited excellent anti-cancer efficacy in LLC-bearing mice.In summary, the current study demonstrates that DHA triggers ferroptosis, facilitating the ICD of lung cancer thereupon. This work reveals for the first time the effect and underlying mechanism by which DHA induces ICD of cancer cells, providing novel insights into the regulation of the immune microenvironment for cancer immunotherapy by Chinese medicine phytopharmaceuticals.
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