从中药中寻找逆转化疗耐药的活性物质，对乳腺癌的临床治疗具有重要意义。重楼在云南品种多、种植广。重楼皂苷I（PPI）是重楼皂苷的主要成分，可增敏肝癌和肺癌细胞对化疗的敏感性。我们前期的研究发现，低细胞毒浓度的PPI能显著逆转人乳腺癌细胞MCF-7/ADM的耐药性。并且，其逆转作用与抑制耐药细胞中磷酸化MAPK和P-gp的高表达有关，且能将耐药细胞的细胞周期阻滞在G0/G1期，但具体的作用机制尚不清楚。Cyclin D1-CDK4/6/RB是调控细胞周期和增殖的重要信号通路，可受MAPK磷酸化而激活。本研究拟通过构建过表达MAPK的乳腺癌细胞，探明MAPK是否通过激活Cyclin D1-CDK4/6/RB介导了乳腺癌耐药；同时，在体外和体内，明确PPI是否通过干预MAPK/Cyclin D1-CDK4/6/RB信号通路来逆转乳腺癌耐药。研究对阐明PPI逆转乳腺癌耐药的机制，实现其可能的临床应用具有重要意义。

Drug resistance is one of the critical reasons that cause breast cancer chemotherapeutic failure and clinical relapse. It is of great importance to find new reversal agents from traditional Chinese medicine. Chong-lou is abundant and well cultivated in Yunnan province. Polyphyllin I (PPI) is the most abundant steroidal saponin of Chong-lou, which shows chemosensitive ability in liver and lung cancer cells. Our previous study demonstrated that low cytotoxic concentration of PPI remarkably reversed resistance of MCF-7/ADM cells. This reversal effect emerged with inhibition of a high expression of MAPK and P-gp in resistant breast cancer cells, together with G0/G1 cell cycle arrest. However, the mechanism is unclear. Cyclin D1-CDK4/6/RB pathway plays an important role in cell cycle progression and proliferation. In this study, overexpression of MAPKs in MCF-7 cells will be established to explore whether Cyclin D1-CDK4/6/RB is involved in MAPK mediated resistance. Meanwhile, effect of PPI on MAPK/Cyclin D1-CDK4/6/RB signaling pathway will be studied both in viro and in vivo to well characterize mechanism of action of PPI. This will provide fundamental theories for both basic study and clinical use of PPI.