课题基金基金详情
黄芪通过TNF-α/HIF-1α/iNOS通路防护重离子辐射肺癌相关BMSCs基因组损伤作用及机制研究
结题报告
批准号:
82004094
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
张利英
依托单位:
学科分类:
中西医结合基础理论
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
张利英
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中文摘要
重离子是肺癌放疗的优选射线,但辐射旁效应(RIBE)可导致肺癌微环境重要间质细胞BMSCs基因组损伤而影响其临床应用。基因芯片结果提示可能与TNF-α/HIF-1α/iNOS有关,但未充分证实。中医学认为辐射可耗气伤津、病及精元,通过脏腑互传导致BMSCs精气虚损,营卫失调。课题组前期证明有益气补虚功效的黄芪防护效果明显但物质基础未明。本研究拟通过细胞实验研究重离子辐射肺癌相关BMSCs基因组损伤中TNF-α、HIF-1α和iNOS的分子机制;借助分子对接虚拟筛选能与关键靶蛋白(TNF-α、HIF-1α、iNOS)结合的黄芪小分子;微量热泳动及细胞实验筛选黄芪小分子最佳配伍并进一步从动物、细胞、分子水平探究其对重离子辐射肺癌致BMSCs基因组损伤的保护作用,揭示黄芪多点显效、协同增效防护重离子辐射肺癌相关BMSCs基因组损伤的物质基础及分子机制,为中医药联合辐射治疗肺癌提供理论依据。
英文摘要
Heavy ions are the preferred radiation for lung cancer radiotherapy, but radiation-induced bystander effect (RIBE) can cause damage to the genome of bone marrow mesenchymal stem cells (BMSCs), an important interstitial cell in the lung cancer microenvironment, and affect its clinical application. Gene chip results suggest that it may be related to TNF-α/HIF-1α/iNOS signaling pathway, but it has not been fully confirmed. According to traditional Chinese medicine, radiation can consume Qi, injure body fluid, disease and essence, and lead to deficiency of essence and Qi and maladjustment of camp and health of BMSCs through mutual transmission of viscera. At the early stage of our research group, it has been proved that the protective effect of Astragalus membranaceus is obvious, but the material basis is not clear.This study intends to study the molecular mechanism of TNF-α, HIF-1α and iNOS in the genome injury of BMSCs associated with heavy ion radiation lung cancer through cell experiments.Virtual screening of effective Astragalus molecules that can bind to key target proteins (TNF-α, HIF-1α, iNOS) through molecular docking. Microthermophoresis and cell experiments screened the best compatibility of Astragalus small molecules and further explored its protective effect on the BMSCs genome damage caused by heavy ion radiation lung cancer from animal, cellular and molecular levels and to reveal the material basis and molecular mechanism of multi-point and synergistic protection of Astragalus membranaceus membranaceus against the genomic damage of BMSCs related to heavy ion radiation lung cancer, so as to provide a reference for the treatment of lung cancer by combination of traditional Chinese Medicine.
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DOI:doi.org/10.3389/fimmu.2021.810286
发表时间:2022
期刊:Frontiers in Immunology
影响因子:7.3
作者:Zhiwei Liu;Yiming Zhang;Liying Zhang;Ting Zhou;Yangyang Li;Gucheng Zhou;Zhiming Miao;Ming Shang;Jinpeng He;Nan Ding;Yongqi Liu
通讯作者:Yongqi Liu
Carbon ion radiotherapy triggers immunogenic cell death and sensitizes melanoma to anti-PD-1 therapy in mice.
碳离子放射疗法引发小鼠免疫原性细胞死亡并使黑色素瘤对抗 PD-1 疗法敏感
DOI:10.1080/2162402x.2022.2057892
发表时间:2022
期刊:Oncoimmunology
影响因子:7.2
作者:Zhou H;Tu C;Yang P;Li J;Kepp O;Li H;Zhang L;Zhang L;Zhao Y;Zhang T;Sheng C;Wang J
通讯作者:Wang J
DOI:10.11844/cjcb.2021.01.0002
发表时间:2021
期刊:中国细胞生物学学报
影响因子:--
作者:周谷城;张利英;张苡铭;周婷;李洋洋;牛帆;刘永琦
通讯作者:刘永琦
DOI:10.13748/j.cnki.issn1007-7693.2022.14.018
发表时间:2022
期刊:中国现代应用药学
影响因子:--
作者:张尚祖;刘永琦;李洋洋;陈琰;刘志伟;谢定雄;张利英
通讯作者:张利英
DOI:10.16605/j.cnki.1007-7847.2020.04.0175
发表时间:2021
期刊:生命科学研究
影响因子:--
作者:张利英;张苡铭;周妮娜;卢志伟;丁楠;华君瑞;李洋洋;周婷;刘颖;刘永琦
通讯作者:刘永琦
基于EGFR、HIF-1α和DNA-PKcs靶点组合研究黄芪改善肺癌放疗抵抗的物质基础及分子机制
  • 批准号:
    --
  • 项目类别:
    地区科学基金项目
  • 资助金额:
    33万元
  • 批准年份:
    2022
  • 负责人:
    张利英
  • 依托单位:
国内基金
海外基金