Wnt/β-catenin信号通路的异常不仅和胚胎发育更和肿瘤等疾病的发生关系密切，因此探寻拮抗该信号通路的分子成为肿瘤治疗领域一个炙热的话题。前期研究结果表明汉黄芩素具有较强的抗肿瘤作用，可通过Wnt通路抑制肿瘤血管通透性及阻滞细胞周期，其分子机制并不十分清楚。且这些结果主要基于体外培养肿瘤细胞及其异体移植，亟待利用整体动物模型深入研究汉黄芩素的作用机理。最近几年越来越多的研究者利用果蝇整体动物模型研究肿瘤的致病机理及药物的作用机制。有关汉黄芩素利用果蝇模型研究其抗肿瘤作用机制国内外未见报道。本研究拟以果蝇为模式生物，应用果蝇遗传学、分子生物学和细胞生物学等手段，研究汉黄芩素对Wnt信号通路的干预，寻找其可能靶点，利用体内模型深入阐明汉黄芩素在肿瘤细胞增殖、凋亡及迁移作用等方面的分子机制，综合评价汉黄芩素通过Wnt信号通路对肿瘤发展的影响，从而为汉黄芩素的临床应用提供理论依据。

The Wnt signaling cascade plays essential roles throughout development and adult life of all animals. In parallel, aberrant Wnt signaling underlies a wide range of pathologies in humans including cancer. Myriad proof of studies strongly suggest that interfering with this signal represents an opportunity for rational cancer therapy. We and others have previously shown that wogonin play a potent anti-cancer effects, however, the underlying mechanisms remain poorly understood. In addition, we have demonstrated that wogonin inhibits vascular permeability and tumor proliferation via Wnt signaling pathway. Among the most of date was performed in cultured cell line and axenograft model, it’s necessary to in-depth study the molecular mechanism with a whole-animal model. Recently, accumulated studies have highlighted the power of D. melanogaster for investigating cooperative interactions between tumour suppressors and oncogenes, and for generating in-vivo models of tumour development and metastasis. In this grant application, we propose to set up several tumor-related model in flies, and make use of a series of assays in vitro and in vivo to further study in detail the potential target of wogonin on Wnt signaling cascade, to understand its mechanism on proliferation, cell death and metastasis. We aim to present the theoretical basis for its clinical application and new drug development.