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脂质组分析揭示了辐射诱导肺肿瘤中甘油磷脂不饱和程度的重塑。

Lipidome analyses reveal radiation induced remodeling of glycerophospholipid unsaturation in lung tumor.

机构信息

Department of Radiotherapy, Shenzhen Traditional Chinese Medicine Hospital, The Forth Clinical Medical College, Guangzhou Traditional Chinese Medicine University, Shenzhen, China.

Department of Radiation Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China.

出版信息

Front Immunol. 2024 Oct 24;15:1470269. doi: 10.3389/fimmu.2024.1470269. eCollection 2024.

DOI:10.3389/fimmu.2024.1470269
PMID:39512339
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11540637/
Abstract

Radiotherapy is a pivotal treatment for lung cancer, significantly impacting tumor control and patient quality of life. Despite its benefits, the molecular mechanisms underlying radiotherapy-induced biological alterations in lung cancer cells remain inadequately understood. In this study, we employed a mass spectrometry-based lipidomics approach to investigate lipid profile changes in a lung cancer mouse model post-radiation. Lewis lung carcinoma (LLC) cells were injected into C57BL/6J mice, followed by radiation treatment with varying split doses. Our results showed an increase in sterol lipids and a decrease in glycerolipids, specifically triacylglycerides, indicating disrupted lipid storage. Additionally, we observed significant changes in glycerophospholipid unsaturation, suggesting a remodeling of membrane properties that may influence cell survival. Linear regression analysis demonstrated a significant negative correlation between glycerophospholipid unsaturation index and tumor weight, indicating a potential role in radiation-induced tumor cell death. These findings provide new insights into the lipid metabolic pathways affected by radiotherapy and could inform the development of improved therapeutic strategies for lung cancer treatment.

摘要

放射疗法是肺癌的重要治疗方法,对肿瘤控制和患者生活质量有重大影响。尽管有这些好处,但放射治疗引起肺癌细胞生物学改变的分子机制仍了解不足。在这项研究中,我们采用基于质谱的脂质组学方法来研究肺癌小鼠模型在放射后的脂质谱变化。将 Lewis 肺癌(LLC)细胞注入 C57BL/6J 小鼠,然后进行不同分割剂量的放射治疗。我们的结果显示固醇脂质增加,甘油脂质减少,特别是三酰基甘油,表明脂质储存受到破坏。此外,我们观察到甘油磷脂不饱和程度的显著变化,表明膜性质的重塑可能影响细胞存活。线性回归分析表明甘油磷脂不饱和指数与肿瘤重量之间存在显著负相关,表明其在放射诱导的肿瘤细胞死亡中可能发挥作用。这些发现为放射治疗影响的脂质代谢途径提供了新的见解,并为开发治疗肺癌的改进治疗策略提供了信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/10e8e5fc5ca1/fimmu-15-1470269-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/dab5698dbf3d/fimmu-15-1470269-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/54b4495b7400/fimmu-15-1470269-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/13f79d06a0c7/fimmu-15-1470269-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/8205b6a47bae/fimmu-15-1470269-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/ea980f9960b3/fimmu-15-1470269-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/7a2cbb573322/fimmu-15-1470269-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/10e8e5fc5ca1/fimmu-15-1470269-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/dab5698dbf3d/fimmu-15-1470269-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/54b4495b7400/fimmu-15-1470269-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/13f79d06a0c7/fimmu-15-1470269-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/8205b6a47bae/fimmu-15-1470269-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/ea980f9960b3/fimmu-15-1470269-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/7a2cbb573322/fimmu-15-1470269-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9375/11540637/10e8e5fc5ca1/fimmu-15-1470269-g007.jpg

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本文引用的文献

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Exp Mol Med. 2024 May;56(5):1066-1079. doi: 10.1038/s12276-024-01222-1. Epub 2024 May 1.
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Plasma Lipidomics Profiling to Identify the Biomarkers of Diagnosis and Radiotherapy Response for Advanced Non-Small-Cell Lung Cancer Patients.血浆脂质组学分析以鉴定晚期非小细胞肺癌患者的诊断和放疗反应生物标志物
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Advances and challenges in the treatment of lung cancer.
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Modulation of tumor-associated macrophage activity with radiation therapy: a systematic review.放疗调控肿瘤相关巨噬细胞活性的系统评价。
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