title: Downregulation of ASPP2 in pancreatic cancer cells contributes to increased resistance to gemcitabine through autophagy activation.
abstract: BACKGROUND
  Apoptosis-stimulating of p53 protein 2 (ASPP2) is one of the ASPP family members and it has been reported to be associated with human cancer. However, the role of it in pancreatic cancer is still not clear.
  
  
  METHODS
  We analyzed the expression level of ASPP2 in cancer tissue samples with RT-qPCR, Western Blotting assay and immunohistochemistry staining. We studied the biological function of ASPP2 and its mechanism with gene overexpression and gene silencing technologies. We determined the sensitivity of pancreatic cells with differential ASPP2 level to gemcitabine and whether autophagy inhibition affected the gemcitabine resistance, both in vitro and in vivo.
  
  
  RESULTS
  Expression of ASPP2 was downregulated in cancerous tissues in comparison with para-cancerous tissues. ASPP2 expression was linked to clinical outcomes in patients and down-regulation of ASPP2 increased cell proliferation, autophagic flux, the activity of AMP Kinase of pancreatic cancer cells and vice versa. Knockdown of ASPP2 results in increased resistance to gemcitabine, which was attributed to the enhanced autophagy.
  
  
  CONCLUSIONS
  ASSP2 expression is lower in cancerous tissues and decreased ASPP2 lead to higher cancer cells proliferation and autophagic flux, which contribute to the gemcitabine resistance.
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. smmusb@126.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Nephrology, Changhai Hospital, Second Military Medical University, Changhai Road No.168, Shanghai, China. angelbq@126.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Bian
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. yijie06@medmail.com.cn.
authors.forename: Yi-Jie
authors.initials: YJ
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. schhao88@gmail.com.
authors.forename: Cheng-Hao
authors.initials: CH
authors.lastname: Shao
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. li_gang169@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. laa2001@163.com.
authors.forename: An-An
authors.initials: AA
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. jingwei7777@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Jing
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. liuruichanghai@163.com.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. yingqizhou@163.com.
authors.forename: Ying-Qi
authors.initials: YQ
authors.lastname: Zhou
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. jingang@sohu.com.|Department of Nephrology, Changhai Hospital, Second Military Medical University, Changhai Road No.168, Shanghai, China. jingang@sohu.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Jin
authors.affiliation: Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China. xianguihu@163.com.|Department of Nephrology, Changhai Hospital, Second Military Medical University, Changhai Road No.168, Shanghai, China. xianguihu@163.com.
authors.forename: Xian-Gui
authors.initials: XG
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D000093542:Gemcitabine
chemical_list: D051017:Apoptosis Regulatory Proteins; D034741:RNA, Small Interfering; C090468:TP53BP2 protein, human; D003841:Deoxycytidine; D000093542:Gemcitabine