基于小窝蛋白的汉黄芩素调控肿瘤细胞上皮—基质代谢耦联的抗肿瘤作用机制研究

Targeting the energy metabolism of tumor cells is one of the hotspots of current scientific researches. The Warburg effect in tumor cells is the most obvious characteristic differs from normal cells in energy metabolism. The epithelial-stromal metabolic coupling, which is also called the Reverse Warburg effect, emphasizes the correlation established by the energy metabolism of tumor cells and tumor stroma, and expounds the characteristics of energy metabolism in the tumor microenvironment. Moreover, loss of caveolin-1 in tumor stroma is the key to start the reverse Warburg effect. Previous studies have shown that, the suppression of wogonin on the Warburg effect in tumor cells lead to its antitumor effects. While the study of wogonin in regulating epithelial-stromal metabolic coupling has not been reported yet. This thesis focuses on the biological effect of epithelial stromal metabolic coupling, and investigates the role of caveolin-1 in the relationship of energy metabolism between tumor stroma and tumor cells, and explores that how does wogonin influence the concrete links of energy transfer between tumor stromal cells and tumor cells, finally achieves the purpose of inhibiting tumor growth. This thesis aims to provide a new idea for the research on the antitumor effect of wogonin.

靶向调控肿瘤细胞生长的能量代谢反应是当前科学家研究的热点之一，其中Warburg效应是肿瘤细胞在能量代谢方面区别于正常细胞最明显的特征。而上皮-基质代谢耦联又称逆转warburg效应，则强调了肿瘤细胞和肿瘤基质间通过能量代谢所建立的寄生关系，阐明了肿瘤微环境的能量代谢特征，同时肿瘤基质中小窝蛋白caveolin-1的缺失，是启动逆转warburg效应的关键环节。前期研究表明，汉黄芩素的抗肿瘤作用与其抑制肿瘤细胞的warburg效应，进而抑制肿瘤细胞生长有关，但有关汉黄芩素在上皮基质代谢耦联方面的作用国内外未见报道。本课题重点围绕上皮基质代谢耦联的生物学效应，研究caveolin-1在肿瘤基质和肿瘤细胞之间能量代谢的相互关系中的作用，同时探索汉黄芩素是如何影响肿瘤基质细胞与肿瘤细胞之间能量传递的具体环节，最终实现抑制肿瘤生长的目的，寻找可能的有效影响因子，为汉黄芩素的抗肿瘤作用提供新思路。