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NF-κB介导的炎症调控通路在苦参碱抗白血病作用中的分子机制研究

NF-κB介导的炎症调控通路在苦参碱抗白血病作用中的分子机制研究
  • 导航:首页 > 科学基金
  • 批准号:81673644
  • 批准年度: 2016年
  • 学科分类:中药抗肿瘤药理(H2810) |
  • 项目负责人:马玲娣
  • 负责人职称:副研究员
  • 依托单位:广州医科大学
  • 资助金额:57万元
  • 项目类别:面上项目
  • 研究期限:2017年01月01日 至 2020年12月31日
  • 中文关键词: NF-κB;炎症;苦参碱;白血病
  • 英文关键词:matrine;Leukemia;Signal transducer and activator of transcription 3;Nuclear Factor κB;Interleukin 6

项目摘要

中文摘要

NF-κB是联系炎症与肿瘤的关键核转录因子,其下游靶基因IL-6在白血病发生过程中发挥重要功能。苦参碱是中药苦参中分离出的一种生物碱,具有较为明确的抗炎抗肿瘤活性,但其是否通过NF-κB通路发挥抗肿瘤作用目前尚不清楚。我们的前期研究发现,苦参碱可显著抑制人白血病K562细胞增殖,降低其IL-6表达,同时抑制细胞内NF-κB及JAK2、STAT3的磷酸化。我们推测:苦参碱可能通过抑制NF-κB转录活性下调IL-6表达及其下游的JAK/STAT3通路活性,发挥抗白血病作用。本项目拟以苦参碱处理的白血病细胞为模型,从分子、细胞和整体动物水平确认苦参碱对NF-κB表达及转录活性作用,探讨NF-κB及其介导的IL-6/JAK/STAT3通路在苦参碱抗白血病作用中的分子机制,以期阐明苦参碱的抗白血病作用机制,为探索白血病治疗新策略提供实验依据。

英文摘要

Nuclear factor NF-κB functions as a central point linking inflammation and cancer. Its downstream targeted gene interleukin 6 (IL-6) and IL-6-mediated JAK/STAT3 signaling pathway plays an important role in leukemogenesis. Matrine is an alkaloid compound purified from Sophora flavescensm, which shows anti-inflammatory and anti-cancer acivities both in vitro and in vivo. However, the exact molecular targets or pathways contribute to its anti-cancer activities remains unclear. Our previous study found treatment with matrine could suppress the cell proliferation of human myeloid leukemia cells K562 significantly and down-regulate the expression of IL-6 in both transcriptional and protein level. Further investigations found that matrine could down-regulate the phosphorylation of STAT3 and JAK2 as well as that of nuclear factor κB(NF-κB). Based on these,findings, it is speculated that the anti-leukemia effects of matrine might be mediated via its regulating the activities of NF-κB signaling cohort in leukemia cells. In the present study, we aim to further validate the exact role of matrine in regulating the activities of NF-κB/IL-6 signaling cohort in molecular, cellular and mice model levels by using a matrine-treated leukimia cells model based studies. The findings in this study would decipher the molecular mechanisms via which matrine exert its anti-leukemia effect and shed some light on building novel strategies for treatment of leukemia.

评估说明

    国家自然科学基金项目“NF-κB介导的炎症调控通路在苦参碱抗白血病作用中的分子机制研究”发布于爱科学iikx,并永久归类于相关科学基金导航中,仅供广大科研工作者查询、学习、选题参考。国科金是根据国家发展科学技术的方针、政策和规划,以及科学技术发展方向,面向全国资助基础研究和应用研究,发挥着促进我国基础研究源头创新的作用。国科金的真正价值在于它能否为科学进步和社会发展带来积极的影响。

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