title: Insulin-like growth factor 1 receptor promotes the growth and chemoresistance of pancreatic cancer.
abstract: BACKGROUND
  Insulin-like growth factor 1 receptor (IGF1R) plays important roles in the progression of pancreatic cancer. However, the underlying mechanism remains unclear.
  
  
  OBJECTIVE
  The purpose of this study was to investigate the effects of IGF1R knockdown on the proliferation, apoptosis and chemosensitivity of pancreatic cancer cells, and explore the possible mechanisms.
  
  
  METHODS
  Pancreatic cancer cells expressing IGF1R shRNA were established, and the cell proliferation, colony formation, and chemosensitivity to gemcitabine were examined in vitro. The activation of AKT and NF-κB was detected by Western blot analysis and luciferase assay, respectively. Xenograft mice models were established to evaluate the in vivo anti-tumor effects of IGF1R knockdown.
  
  
  RESULTS
  IGF1R knockdown notably inhibited pancreatic cancer cell proliferation and colony formation, induced apoptosis, and inhibited xenograft tumor growth. Moreover, IGF1R knockdown significantly enhanced chemosensitivity to gemcitabine in pancreatic cancer cells, and this was correlated with the inhibition of PI3K/AKT and NF-κB pathways.
  
  
  CONCLUSIONS
  IGF1R knockdown suppresses tumor growth and enhances chemosensitivity in pancreatic cancer via the inhibition of PI3K/AKT and NF-κB pathways, and is a promising approach to overcome the chemoresistance of pancreatic cancer.
authors.affiliation: Department of General Surgery, Peking University First Hospital, 8th Xishiku Street, Xicheng District, Beijing, 100034, People's Republic of China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Tian
authors.forename: Kun
authors.initials: K
authors.lastname: Hao
authors.forename: Changfu
authors.initials: C
authors.lastname: Qin
authors.forename: Kun
authors.initials: K
authors.lastname: Xie
authors.forename: Xuehai
authors.initials: X
authors.lastname: Xie
authors.forename: Yinmo
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D055785:Gene Knockdown Techniques; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D016328:NF-kappa B; D034741:RNA, Small Interfering; D003841:Deoxycytidine; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D000093542:Gemcitabine