胰腺癌干细胞是导致肿瘤耐药的一个主要因素，而调控肿瘤干细胞是干预胰腺癌耐药的关键措施。OLA1对多种肿瘤的发生发展均起到调控作用，但是其是否可以通过调控胰腺癌干细胞影响胰腺癌耐药并且其主要的作用机制目前尚不明确。我们的课题组前期工作首次证明，抑制OLA1可以提高胰腺癌细胞对化疗药物吉西他滨的敏感性，并且降低胰腺癌干细胞标志物的表达。Wnt信号通路可以通过调控干细胞影响肿瘤耐药，我们的前期结果也显示OLA1可以抑制Wnt信号通路中的β-catenin。本课题组拟在此基础上，在动物和细胞模型水平，以OLA1为靶点，通过OLA2沉默和过表达联合Wnt信号通路抑制剂或激动剂和干预，探讨OLA1是否可以通过Wnt信号通路调控干细胞影响胰腺耐药，揭示OLA1是否可以作为胰腺癌耐药的治疗靶点，并为临床治疗提供理论依据。

Pancreatic cancer stem cells are one of the main factors leading to drug resistance, and cancer stem cells is the key target to overcome the pancreatic cancer drug resistance. OLA1 is the regulator of cancer development, but it is not clear whether it can affect the drug resistance of pancreatic cancer by regulating cancer stem cells and its main mechanism is unknown. Our preliminary work for the first time proved that inhibiting OLA1 can enhance the sensitivity of pancreatic cancer cells to gemcitabine and reduce the expression of pancreatic cancer stem cell markers. The Wnt signaling pathway plays an important role in cancer stem cells, closely related to the drug resistance. Our preliminary work also show that OLA1 can inhibit the β-catenin involved in Wnt signaling pathway. The present study based on our preliminary work, target by OLA1 gene over-expression or silencing joint with the Wnt signaling pathway inhibitor or agonist, observed whether the OLA1 can affect the drug resistance of pancreatic cancer by regulating Wnt signaling pathway, reveal the OLA1 in treatment of pancreatic cancer drug resistance and provide the theoretical for clinical application.