肿瘤细胞的保护性自噬是耐药的重要机制，抑制细胞自噬可以克服肿瘤细胞的耐药和增强肿瘤细胞对化疗药物的敏感性。前期在国家自然基金项目资助下项目组研究发现，新藤黄酸能够抑制肿瘤细胞自噬，低浓度的新藤黄酸亦能够逆转肿瘤细胞耐药，但其关联性尚未阐明。因此新藤黄酸调控细胞自噬与逆转肿瘤细胞耐药和影响细胞增殖之间的cross-talk值得进一步研究。本课题拟以新藤黄酸调控细胞自噬为着力点，选择亲本与耐药的乳腺癌细胞作为研究对象，采用慢病毒转染基因沉默、信号通路阻断等技术和采用流式细胞仪、激光共聚焦显微镜等分析手段，从体内外两方面探讨新藤黄酸通过影响PTEN-PI3K /AKT信号通路调控细胞自噬，诱导细胞凋亡，从而抑制乳腺癌细胞增殖，逆转乳腺癌细胞耐药的作用和科学内涵，为阐明中西药联合应用协同增效减毒的作用和机制提供一定的理论依据。

The key mechanism of multidrug resistance on tumor cell is involve protective autophagy. Inhibiting autophagy could make tumor cell overcome multidrug resistance and more sensitive to the chemotherapy. The project team’s research by support from the National Nature Science Foundation of China，the results showed that Gambogenic acid (GNA) inhibit tumor cell autophagy, and the low concentration of GNA could reverse the drug resistance of tumor cell. However, the mechanism has not been elucidated. So, the cross-talk molecular mechanism of GNA regulating cell autophagy, reversing tumor cell drug resistance and inhibiting cell proliferation is worthy of further study. This project is planning to focus on autophagy, and to choose human breast cancer cell which is parental and drug resistant as the targets, use lentiviral transfection and signaling pathway inhibition, and analysis methods such as FACS and confocal microscope and so on, then to discuss the cross –talk mechanisms of GNA regulating cell autophagy , inducing cell apoptosis through PTEN-PI3K/AKT signaling pathway, inhibiting human breast cancer cell proliferation and reversing human breast cancer cell drug resistance in vitro and in vivo, which can provides the theoretical basis of the Chinese medicine combined with Western medicine about the increase effect and decrease toxicity.