胰腺癌是恶性程度极高、预后极差的肿瘤，五年生存率不足9%，其主要原因之一在于患者容易对以吉西他滨为主的一线治疗方案产生化疗耐药。因此，研究胰腺癌化疗耐药机制具有重要意义。既往OLR1研究主要集中在心血管及代谢性疾病等领域，在胰腺癌中的作用及机制尚不清楚。本课题组前期研究发现OLR1表达水平在胰腺癌吉西他滨耐药细胞株中明显升高，并且吉西他滨治疗可以诱导胰腺癌PDTX模型中OLR1表达水平升高，提示OLR1可能在胰腺癌化疗耐药中具有重要作用。因此，本研究拟从分子、细胞、动物及临床样本等水平，研究OLR1对胰腺癌增殖、凋亡、侵袭迁移、EMT及化疗敏感性等生物学行为与表型的影响；解析OLR1/c-Myc/HMGA2轴介导胰腺癌吉西他滨化疗耐药的具体机制；探索靶向OLR1逆转胰腺癌吉西他滨化疗耐药的可行性；明确OLR1作为胰腺癌患者化疗预后标志物的潜在临床应用价值。为胰腺癌治疗提供新靶点、新思路。

Pancreatic cancer is one of the most lethal cancers, with five-year survival rate less than 9 %, basically because of the resistance to current chemotherapy represented by gemcitabine. Therefore, revealing the underlying mechanism of resistance to chemotherapy is of great significance. OLR1 was studied mostly in areas of cardiovascular system as well as metabolism diseases, but its role is unclear in pancreatic cancer. Previously, our group demonstrated that OLR1 was obviously upregulated in gemcitabine-resistance cell lines compared to parental cell lines. Moreover, gemcitabine treatment in PDTX model of pancreatic cancer can also induce upregulation of OLR1, indicating its potential role in chemoresistance. Therefore, we will work from several aspects including molecular, cell lines, animal models and clinical samples to explore the role OLR1 plays in pancreatic cancer phenotype, including proliferation, apoptosis, invasion, metastasis, EMT and chemoresistance. In addition, we will investigate the mechanism how OLR1/c-Myc/HMGA2 axis mediates gemcitabine resistance. Furthermore, possible ways to reverse chemoresistance by targeting OLR1 and potential application of OLR1 as a marker for prognosis will also be evaluated, offering new target and method for the treatment of pancreatic cancer.