机构：[1]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street, Beijing 100053, People’s Republic of China普通外科首都医科大学宣武医院[2]Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People’s Republic of China[3]Department of Hepatobiliary Surgery, Binzhou People’s Hospital, Binzhou Medical College, Yantai, Shandong 256600, People’s Republic of China
Pancreatic adenocarcinoma upregulated factor (PAUF) is a new oncogene that activates signaling pathways that play a critical role in resistance to gemcitabine. We thus speculated that PAUF also plays a role in resistance to gemcitabine of pancreatic cancer cells. We established BxPC-3 cell lines with stable PAUF knockdown (BxPC-3_shPAUF) and controls (BxPC-3_shCtrl) and evaluated sensitivity to gemcitabine in vitro by MTT and flow cytometry. We established a xenograft model of human pancreatic cancer to examine PAUF function in gemcitabine resistance in vivo. Gene chip microarrays were performed to identify differentially expressed genes in BxPC-3_shPAUF and BxPC-3_shCtrl cells. Silencing PAUF increased the sensitivity of BxPC-3 cells to gemcitabine in vitro and in vivo. PAUF-knockdown BxPC-3 cell lines treated with gemcitabine showed increased proliferation inhibition and apoptosis compared with controls. Gemcitabine exhibited a more pronounced effect on reduction of BxPC-3_shPAUF tumors than BxPC-3_shCtrl tumors. Terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL) assays confirmed a significantly higher apoptotic rate of BXPC-3_shPAUF tumors compared with BXPC-3_shCtrl tumors. Gene array showed that PAUF function in gemcitabine sensitivity might involve MRP2, MRP3, MDR1, PIK3R1, and NFkB2 genes. PAUF could be considered as a key molecular target for sensitizing pancreatic cancer cells to gemcitabine.
基金：
the National Natural Science Foundation of China (No. 81272756)
Beijing Municipal Administration of Hospitals (No. XMLX201404).
第一作者机构：[1]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street, Beijing 100053, People’s Republic of China
通讯作者：
通讯机构：[1]Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street, Beijing 100053, People’s Republic of China
推荐引用方式(GB/T 7714)：
Chong-chong Gao,Xiao-Lan Xu,Fei Li,et al.Silencing pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer cells to gemcitabine[J].TUMOR BIOLOGY.2016,37(6):7555-7564.doi:10.1007/s13277-015-4641-2.
APA：
Chong-chong Gao,Xiao-Lan Xu,Fei Li,Ben-gang Gong,Shuang Liu...&Hua Jiang.(2016).Silencing pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer cells to gemcitabine.TUMOR BIOLOGY,37,(6)
MLA：
Chong-chong Gao,et al."Silencing pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer cells to gemcitabine".TUMOR BIOLOGY 37..6(2016):7555-7564
