title: Periostin promotes the chemotherapy resistance to gemcitabine in pancreatic cancer.
abstract: Pancreatic ductal adenocarcinoma (PDAC) ranks fourth among cancer-related deaths. The nucleoside analog gemcitabine has been the cornerstone of adjuvant chemotherapy in PDAC for decades. However, gemcitabine resistance develops within weeks of chemotherapy initiation, which might be intrinsic to cancer cells and influenced by tumor microenvironment. Recently, pancreatic stellate cells (PSCs) have greatly increased our attention on tumor microenvironment-mediated drug resistance. Periostin is exclusively overexpressed in PSCs and the stroma of PDAC creating a tumor-supportive microenvironment in the pancreas. However, whether periostin contributed to chemoresistance in PDAC remains unknown. Therefore, we focused on the role of periostin in PDAC by observing the effects of silencing this gene on gemcitabine resistance in vitro and in vivo aiming to explore the possible molecular mechanism. In this study, the pancreatic cancer cell (PCC) proliferation and apoptosis were assayed to investigate the sensitivity to gemcitabine after silencing periostin. We provide the evidence that periostin not only drives the carcinogenic process itself but also significantly associated with gemcitabine-induced apoptosis. These findings collectively indicated that periostin increases the chemoresistance to gemcitabine. Thus, targeting periostin might offer a new opportunity to overcome the gemcitabine resistance of PDAC.
authors.affiliation: Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.affiliation: Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
authors.forename: Lingxi
authors.initials: L
authors.lastname: Xing
authors.affiliation: Department of Instrument Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Qin
authors.affiliation: Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
authors.forename: Xingxin
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
authors.forename: Jiajie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Qiao
authors.affiliation: Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China.
authors.forename: Lizhou
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis and National Ministry of Education, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China. qzhao@shsmu.edu.cn.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhao
authors.affiliation: Department of Ultrasound, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, China. lianfang_du@126.com.
authors.forename: Lianfang
authors.initials: L
authors.lastname: Du
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D016022:Case-Control Studies; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle; D002465:Cell Movement; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D058954:Pancreatic Stellate Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; D012333:RNA, Messenger; D003841:Deoxycytidine; D000093542:Gemcitabine
keywords: Akt; Chemoresistance; Gemcitabine; Pancreatic ductal adenocarcinoma; Periostin