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基于缝隙连接蛋白靶点的青蒿素B对顺铂抗肺癌的增效减毒作用机制研究

基于缝隙连接蛋白靶点的青蒿素B对顺铂抗肺癌的增效减毒作用机制研究
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  • 批准号:81673646
  • 批准年度: 2016年
  • 学科分类:中药抗肿瘤药理(H2810) |
  • 项目负责人:宋丽艳
  • 负责人职称:研究员
  • 依托单位:暨南大学
  • 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: 靶点;青蒿素;顺铂;肺癌;增效
  • 英文关键词:Artemisinin B;Anti-lung cancer;Synergism and detoxication;Gap junction;Connexin

项目摘要

中文摘要

青蒿素B系中药黄花蒿中抗肿瘤活性成分。缝隙连接蛋白(Cx)具肿瘤抑制因子特性,能介导顺铂在肿瘤和非肿瘤细胞中的差异性积累,是极具潜力的抗肿瘤靶点。一线抗肿瘤药物顺铂对肿瘤细胞有着强大杀伤作用但严重的毒副作用成为限制其应用的瓶颈问题。我们前期研究发现:青蒿素B能协同顺铂抑制肺癌细胞的增殖且能改变肺癌细胞中Cx的表达及缝隙连接(GJ)功能,提示其对顺铂抗肺癌方面可能具有“增效减毒”作用且与Cx有关。为解决此科学问题,本项目拟在前期工作基础上,进行如下研究:(1)全面评价青蒿素B对顺铂抗肺癌的“增效减毒”作用;(2)确认青蒿素B“增效减毒”作用是否由Cx介导;(3)探究青蒿素B对Cx及GJ调控的相关信号通路。本项目系国内外首次基于Cx靶点对青蒿素B在抗肿瘤方面“增效减毒”作用机制进行研究,其结果可为青蒿素B的“增效减毒”作用给予科学阐释,并为拓展青蒿素类活性成分新用途提供科学资料。

英文摘要

Artemisinin B is one kind of anti-tumor active ingredient from Artemisia annua. Connexin (Cx) possesses tumor suppressor properties and can be a great potential target for cancer therapy. Cisplatin (DDP) is an antitumor drug in first-line therapy for cancer and can be differentially accumulated in tumor and non-tumor cells, which may be mediated by Cx. DDP has a strong cytotoxic effect on cancer cells, but severe side effects limit its clinical application. In the previous study, we found that Artemisinin B increased the cytotoxicity of DDP, up-regulated expression of Cx and enhanced the function of gap junction (GJ) in lung cancer cells, suggesting that it may have the synergism and detoxication effects in the treatment of lung cancer. To explore of the mechanism of synergism and detoxication effects of Artemisinin B in combination with DDP, the studies will be carried out as follows: (1) Evaluating synergism and detoxication effects of Artemisinin B in combination with DDP; (2) Further investigating if the mechanism involves Cx, GJ and other target proteins; (3) Exploring the signaling pathways involved in the regulation of GJ and Cx by Artemisinin B. The project aims to investigate the synergism and detoxication effects of Artemisinin B and to explore the underlying mechanism associate with Cx. The research findings can provide a scientific interpretation of the synergism and detoxication effects of Artemisinin B in combination with DDP, as well as the scientific information for the new application of artemisinins.

评估说明

    国家自然科学基金项目“基于缝隙连接蛋白靶点的青蒿素B对顺铂抗肺癌的增效减毒作用机制研究”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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