title: Silencing pancreatic adenocarcinoma upregulated factor (PAUF) increases the sensitivity of pancreatic cancer cells to gemcitabine.
abstract: 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.
authors.affiliation: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street, Beijing, 100053, People's Republic of China.
authors.forename: Chong-Chong
authors.initials: CC
authors.lastname: Gao
authors.affiliation: Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Xiao-Lan
authors.initials: XL
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street, Beijing, 100053, People's Republic of China. feili36@ccmu.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary Surgery, Binzhou People's Hospital, Binzhou Medical College, Yantai, Shandong, 256600, People's Republic of China.
authors.forename: Ben-Gang
authors.initials: BG
authors.lastname: Gong
authors.affiliation: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street, Beijing, 100053, People's Republic of China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street, Beijing, 100053, People's Republic of China.
authors.forename: Ye-Qing
authors.initials: YQ
authors.lastname: Cui
authors.affiliation: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street, Beijing, 100053, People's Republic of China.
authors.forename: Hai-Chen
authors.initials: HC
authors.lastname: Sun
authors.affiliation: Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China.
authors.forename: Ping-Yong
authors.initials: PY
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street, Beijing, 100053, People's Republic of China.
authors.forename: Ya-Min
authors.initials: YM
authors.lastname: Zheng
authors.affiliation: Department of General Surgery, Xuanwu Hospital, Capital Medical University, Number 45, Changchun Street, Beijing, 100053, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D020868:Gene Silencing; D006801:Humans; D007124:Immunoenzyme Techniques; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D037102:Lectins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C517340:ZG16B protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Apoptosis; BxPC-3; Gemcitabine resistance; PAUF; Pancreatic cancer