由于三阴性乳腺癌缺乏特定的分子治疗靶点，因此在其治疗上一直面临着严峻的挑战。我们对犬乳腺癌的相关研究发现，AKT蛋白的磷酸化在三阴性乳腺癌中存在异常表达的现象，这表明PI3K/AKT/mTOR可能是调控三阴性犬乳腺癌细胞的重要信号通路之一，有可能成为治疗三阴性犬乳腺癌特定的分子靶点。本课题在前期研究的基础上，从组织学、细胞学、基因和蛋白表达等方面对PI3K/AKT/mTOR信号通路调控三阴性犬乳腺癌的过程和分子机理进行研究，同时探讨PI3K/AKT/mTOR信号通路双向抑制剂NVP-BEZ235协同紫杉醇诱导三阴性犬乳腺癌细胞凋亡的机制。通过建立体内和体外三阴性犬乳腺癌细胞研究模型，重点阐述PI3K/AKT/mTOR信号通路对三阴性犬乳腺癌细胞增殖和凋亡的影响，并通过基因沉默、免疫印迹、免疫染色、流式细胞术等手段进行验证。本研究有望发现三阴性犬乳腺癌的致病机理及新的药物治疗靶点。

Due to the lack of specific molecular target for therapy, the treatment of triple-negative breast cancer (TNBC) is a severe challenge. During the research on canine breast cancer, we found that the phosphorylation of AKT protein was abnormal in triple-negative canine breast cancer(TNCBC), indicating that PI3K/AKT/mTOR may be one of the important signaling pathways in regulating TNCBC cells and could be a specific molecular target for treating TNBC in dogs. On the basis of previous studies, our research will focus on the processes and molecular mechanism of PI3K/AKT/mTOR signal pathway in regulating TNCBC from histology, cytology, gene and protein expression respectively, therefore to explore the mechanism of apoptosis induced by dual PI3K/AKT/mTOR inhibitor cooperated with paclitaxel in TNCBC cells. Through the establishment of TNCBC study model in vivo and in vitro, this project’s main point is elaborating the effects of PI3K/AKT/mTOR signal pathway on proliferation and apoptosis of TNCBC cells, which will be verified by means of gene silencing, Western Blotting, immunostaining, flow cytometry, etc. It is expected to find pathogenic mechanism of TNCBC and new therapeutic targets for drug therapy by this study.