title: High glucose-induced resistance to 5-fluorouracil in pancreatic cancer cells alleviated by 2-deoxy-D-glucose.
abstract: Abnormal glucose metabolism from hyperglycemia or diabetes aggravates the progression of pancreatic cancer. It is unknown whether high glucose has an impact on the antitumor effect of 5-fluorouracil (5-Fu) and whether targeting aberrant glucose metabolism using 2-deoxy-D-glucose (2-DG) may reverse this effect in high-glucose microenvironments. The cell viability of AsPC-1 and Panc-1 was analyzed by MTT assay following 5-Fu treatment at different glucose concentrations. Altered sensitivity to 5-Fu by 2-DG was also analyzed. LY294002 was used to inhibit PI3K-Akt signaling to determine the mechanism involved. In response to glucose, 5-Fu-induced cell growth inhibition was attenuated in a dose-dependent manner, accompanied with activated p-Akt, while 2-DG enhanced 5-Fu-induced cell growth inhibition. Moreover, blocking the PI3K/Akt pathway by LY294002 effectively eliminated 2-DG-induced apoptosis. In conclusion, high glucose weakens the antitumor effect of 5-Fu via PI3K/Akt signaling. Using 2-DG in combination with 5-Fu significantly increased their therapeutic effectiveness in high-glucose microenvironments.
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Diao
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Guo
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xuandi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Surgical Oncology, The First Affiliated Hospital, Xi'an Jiaotong University College of Medicine, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Chengxue
authors.initials: C
authors.lastname: Dang
keywords: 2-deoxy-D-glucose; 5-fluorouracil; glucose; pancreatic cancer