胰腺癌是一种常见的恶性肿瘤，手术切除率低，对化疗高度抵抗，预后极差。凋亡抑制蛋白（inhibitor of apoptosis protein， IAPs）家族中的XIAP 和Survivin在胰腺癌组织中高表达，是胰腺癌化放疗抵抗的重要因子。我们前期研究表明，同时抑制XIAP 和survivin 表达后，胰腺癌细胞的增殖受到显著抑制，成瘤能力减弱，然而化疗药物诱导的细胞凋亡并无预期理想。自噬水平的升高可能是抗IAP治疗效果欠佳的重要原因，PI3K/AKT是调节细胞凋亡和自噬的重要信号通路。本研究拟在同时抑制XIAP及Survivin的基础上加用自噬抑制剂，明确抗IAP的同时抑制自噬能否进一步增加胰腺癌细胞凋亡水平，提高化疗敏感性，并初步探讨PI3K/AKT/mTOR-Beclin1信号通路在介导胰腺癌细胞凋亡和自噬相互作用机制中的作用，以期为临床上改善胰腺癌化疗敏感性寻找新的治疗方法。

Pancreatic cancer(PC) is a common malignant tumor which is characterized by low resection rate,high chemoresistance and poor prognosis.High level expression of XIAP and Survivin (Inhibitor of apoptosis protein)which are the crucial factors in in chemotherapy and radiotherapy resistance of pancreatic cancer are observed in pancreatic cancer Our previous studies have shown that the proliferation and tumorigenicity of pancreatic cancer cells were significantly inhibited while the chemotherapy-induced apoptosis had not expected after the inhibition of XIAP and Survivin. Since elevated levels of autophagy may be an important cause of poor treatment of anti-IAP, PI3K / AKT is an important signaling pathway regulating apoptosis and autophagy In this study, we will add the inhibitor of autophagy on the basis of inhibition of XIAP and Survivin in order to make sure that if this can further increase the level of apoptosis of pancreatic cancer cells,enhance chemosensitivity and explore the role of PI3K / AKT / mTOR-Beclin1 signaling pathway in mediating the interaction mechanism of apoptosis and autophagy in pancreatic cancer ,aiming to find a new way for improving the clinical sensitivity of pancreatic cancer chemotherapy treatment.

胰腺癌是一种常见的恶性肿瘤，手术切除率低，对化疗高度抵抗，预后极差。凋亡抑制蛋白（inhibitor of apoptosis protein， IAPs）家族中的XIAP 和Survivin在胰腺癌组织中高表达，是胰腺癌化放疗抵抗的重要因子。我们前期研究表明，同时抑制XIAP 和survivin 表达后，胰腺癌细胞的增殖受到显著抑制，成瘤能力减弱，然而化疗药物诱导的细胞凋亡并无预期理想。自噬水平的升高可能是抗IAP治疗效果欠佳的重要原因。 本研究中我们通过对稳定抑制XIAP和Survivin的细胞株自噬水平的检测，发现在同时抑制XIAP和Survivin表达后，胰腺癌细胞自噬水平升高，与实验预期结果一致，进一步证实了我们前期研究中同时抑制XIAP和Survivin后化疗药物诱导的细胞凋亡并无预期理想的原因。为我们后期在同时抑制XIAP和Survivin的基础上加用自噬抑制剂研究胰腺癌细胞化疗敏感性变化及机制研究提供基础，为临床抗IAP治疗联合自噬抑制治疗胰腺癌提供科学依据。