业已证实，飞燕草素（delphinidin）不但具有较强的抗癌作用，而且能诱导肿瘤细胞产生保护性自噬反应。但delphinidin联合自噬抑制剂能否增强抗HER-2阳性乳腺癌效应？尚未证实。项目组前期发现，delphinidin能与HER-2受体结合，预实验提示delphinidin抑制MDA-MB-453细胞增殖能力，降低LC3-I/LC3-Ⅱ比值。本项目在此基础上，首先运用移植瘤模型和细胞模型，体内体外进一步证实delphinidin通过阻断MAPK和NF-κB通路抗HER-2阳性乳腺癌的分子机制；然后体外探讨delphinidin通过阻断mTOR通路以及活化MAPK通路诱导自噬；最后体内体外研究靶向自噬抑制，增加HER-2阳性乳腺癌对delphinidin的敏感性。研究结果不但明确delphinidin抗HER-2阳性乳腺癌的分子机制，而且从细胞应答角度为肿瘤化疗增敏提供新措施。

It has been demonstrated that delphinidin not only has potential anti-cancer effects, but also induce tumor cells autophagy which is a self protective response under stress conditions. However, it is still unknown whether delphinidin synergistically inhibit HER-2 positive breast cancer with autophagy inhibitor. Our previous studies have been suggested that delphinidin can combine with HER-2 receptor, and the preliminary experiment suggested that delphinidin also can inhibit the proliferative ability of MDA-MB-453 breast cancer cell, down-regulate the ratio of LC3-Ⅰ/LC3-Ⅱ. In the present study, we will first utilize HER-2 positive breast cancer cells (in vitro) and xenograft model (in vivo) to further verify the inhibitory effect in breast cancer by blocking the MAPK and NF-κB pathways mediated by HER-2 receptor. Then, we investigate the delphinidin-induced autophagy by blocking mTOR and activating MAPK pathway. Finally, we explore the autophagy inhibition in vitro and in vivo to increase the sensitivity of HER-2 positive breast cancer on delphinidin. The results will not only further clarify the inhibitory effect and the underlying molecular mechanism of delphinidin in HER-2 positive breast cancer, but also provide a new strategy in tumor treatment through targeting autophagy inhibition.