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乳腺癌前病变PGC-1β/ERRα信号轴调控糖代谢重组的作用及乳岩内消霜外用干预机制

乳腺癌前病变PGC-1β/ERRα信号轴调控糖代谢重组的作用及乳岩内消霜外用干预机制
  • 导航:首页 > 科学基金
  • 批准号:81673979
  • 批准年度: 2016年
  • 学科分类:中医外科(H2709) |
  • 项目负责人:马民
  • 负责人职称:教授
  • 依托单位:暨南大学
  • 资助金额:66万元
  • 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: 乳腺癌;PGC-1β/ERRα;代谢;乳岩;干预
  • 英文关键词:Breast Precancerous Lesion ;PGC-1 beta /ERR alpha Signaling Axis ;Glucose Metabolic Reprogramming ;R

项目摘要

中文摘要

PGC-1β/ERRα信号轴是调控乳腺组织癌变过程中糖代谢重组的核心机制,与乳腺组织癌变密切相关。前期研究证实乳岩内消霜外用对乳腺癌前病变具有良好治疗作用,可显著下调癌前病变组织细胞PGC-1β、ERRα蛋白水平,抑制OXPHOS及有氧糖酵解途径SDHB、HK-2等表达,提示其良好疗效与通过该信号轴调节乳腺癌前病变糖代谢重组密切相关。本项目通过DMBA联合雌孕激素序贯诱导动物模型,采用基因芯片、免疫印迹和液质联用等技术,检测该信号轴和糖代谢重组关键信号分子PGC-1β、ERRα、HIF-1α等变化水平,明晰该信号轴调控乳腺癌前病变糖代谢重组的核心机制及介导乳岩内消霜通过该轴调节糖代谢重组的关键信号分子。并利用MCF-10AT细胞模型,阻断或沉默关键信号分子进行确证。此研究可进一步揭示乳腺癌前病变发生发展的分子机制,及该霜有效外治乳腺癌前病变和预防、阻断乳腺癌发生发展的作用机理甚至作用靶点。

英文摘要

The Signaling Axis of PGC-1 beta /ERR alpha is the core mechanism in regulating glucose metabolism reprogramming during the carcinogenesis of breast, which indicates a close relation with breast cancer. Previous studies have confirmed that the external use of Ruyanneixiao Cream has an excellent therapeutic effect on breast precancerous lesions, which could significantly down- regulate PGC-1 beta and ERR alpha protein levels and inhibit the expression of SDHB, HK2,etc in the OXPHOS and aerobic glycolysis pathway, suggesting that this beneficial effect of Ruyanneixiao Cream may be closely related to that the signaling axis of PGC-1 beta/ERR alpha regulates glucose metabolic reprogramming in breast precancerous lesions. This project detects the key signaling molecules PGC-1 beta, ERR alpha and HIF-1 alpha levels of this signaling axis and glucose metabolism reprogramming on animal models induced by DMBA combined the sequential therapy of estrogen and progesterone by gene chip,Western blot and LC-MS,to clarify the core mechanisms that PGC-1 beta/ERR alpha signaling axis regulates the glucose metabolism reprogramming in breast precancerous lesions and the key signaling molecules of the signaling axis in regulating the glucose metabolism reprogramming mediated by Ruyanneixiao Cream. And to confirm this mechanism by blocking or silencing the key signaling molecules in the MCF-10AT cell model. This study may further clarifies breast precancerous lesions pathogenesis and reveals the mechanism and even targets of Ruyanneixiao Cream for effective external treatment in breast precancerous lesions and preventing and blocking the development of breast cancer.

评估说明

    国家自然科学基金项目“乳腺癌前病变PGC-1β/ERRα信号轴调控糖代谢重组的作用及乳岩内消霜外用干预机制”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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