Association between oxidative stress, mitochondrial function of peripheral blood mononuclear cells and gastrointestinal cancers

Journal of Translational Medicine

Research

Hua Li¹  Min Jin²  Dong Yang²  Zhaoli Chen²  Xinxing Wang²  Junwen Li²  Xuelian Zhang²  Zhiqiang Shen²  Weili Liu²  Zilin Wei²  Yuan Gao³ 

[1]Department of Endoscopy, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

[2]Tianjin Institute of Environmental and Operational Medicine, Tianjin, China

[3]Tianjin Institute of Environmental and Operational Medicine, Tianjin, China

[4]Maternity & Child Care Center of Dezhou, Dezhou, Shandong, China

关键词: Gastrointestinal cancers;    PBMCs;    Mitochondrial dysfunction;   

DOI  :  10.1186/s12967-023-03952-8

 received in 2022-10-11, accepted in 2023-02-01,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundThe incidence and mortality rate of gastrointestinal cancers are high worldwide. Increasing studies have illustrated that the occurrence, progression, metastasis and prognosis of cancers are intimately linked to the immune system. Mitochondria, as the main source of cellular energy, play an important role in maintaining the physiological function of immune cells. However, the relationship between mitochondrial function of immune cells and tumorigenesis has not yet been systematically investigated.MethodsA total of 150 cases, including 60 healthy donors and 90 primary gastrointestinal cancer patients without anti-tumor treatments (30 with gastric cancer, 30 with liver cancer and 30 with colorectal cancer) were involved in our study. The oxidant/antioxidant and cytokine levels in plasma, the ROS level, mitochondrial function and apoptosis ratio of peripheral blood mononuclear cells (PBMCs) were evaluated.ResultsThe imbalance between oxidant and antioxidant in plasma was discovered in the primary gastrointestinal cancer patients. The levels of cell reactive oxygen species (ROS) and mitochondrial ROS in PBMCs of primary gastrointestinal cancers were significantly increased compared with that in healthy donors. Meanwhile, the ATP content, the mtDNA copy number and the mitochondrial membrane potential (MMP) in PBMCs of patients with primary gastrointestinal cancers were lower than those in control group. The decreased MMP also occurred in immune cells of gastrointestinal cancers, including T cell, B cell, NK cell and monocyte. Furthermore, the PBMCs apoptosis ratio of primary gastrointestinal cancer patients was significantly higher than that of control group. Importantly, an increase of IL-2 and IL-6 and a decrease of IgG in plasma were found in the patients with primary gastrointestinal cancers. These changes of mitochondrial function in immune cells were consistent among primary gastrointestinal cancers without anti-tumor treatments, such as liver cancer, gastric cancer and colorectal cancer.ConclusionOur study demonstrated that the imbalance of oxidation/antioxidation in primary gastrointestinal cancer patients without anti-tumor treatments results in excessive ROS. The oxidative stress was associated to the mitochondrial dysfunction, the apoptosis of immune cells and eventually the abnormal immune function in primary gastrointestinal cancers. The application of immune cell mitochondrial dysfunction into clinical evaluation is anticipated.

【 授权许可】

CC BY   
© The Author(s) 2023

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