以吉西他滨为基础的单药或联合方案是目前胰腺癌化疗的首选。我们前期证明，hENT1是影响胰腺癌对吉西他滨化疗敏感性的一个重要分子；深入研究发现，FBW7能通过溶酶体降解途径影响hENT1的蛋白水平及细胞膜定位，进而影响胰腺癌对吉西他滨的化疗敏感性；基于蛋白-蛋白相互作用分析及前期研究提示，我们又推测ARF6介导了hENT1的“细胞膜－溶酶体”转位，是FBW7通过溶酶体降解途径调控hENT1表达的中间分子，由此提出“FBW7/ARF6/hENT1”这一新的通路。针对这一通路，我们拟进一步开展体内外和临床样本的验证及干预研究，为临床上胰腺癌化疗耐药提供干预和预测的潜在靶点。

Gemcitabine alone and gemcitabine-based combination regimens are generally accepted as the standard chemotherapeutic choice for pancreatic cancer. We previously demonstrated that hENT1 played an important role in impacting on the chemotherapeutic response of gemcitabine in pancreatic cancer. Further studies indicated that FBW7 was involved in protein level regulation and membrane localization of hENT1 by lysosomal degradation pathway to influence the chemosensitivity of gemcitabine in pancreatic cancer. Based on our previous study about the protein interactions, we speculated that ARF6 might work as a connected molecular between FBW7 and lysosome degradative hENT1 by mediating the “membrane to lysosome” translocation of hENT1. Thus, we suggest that there is a new molecular mechanism as an axis of FBW7/ARF6/hENT1 to take effect. We are going to carry out some researches to disturb this functional axis by in vitro and in vivo assays and validation of clinical specimens, which could help effectively predicting the chemoresistance and serve as a potential therapeutic target in pancreatic cancer.