title: Metformin suppresses sonic hedgehog expression in pancreatic cancer cells.
abstract: OBJECTIVE
  Metformin use has previously been associated with decreased cancer risk. The Hedgehog signaling pathway is a well-characterized early and late mediator of pancreatic cancer oncogenesis. The aim of the present study was to clarify the effect of metformin on factors involved in Hedgehog signaling.
  
  
  METHODS
  BxPC3 human pancreatic cancer cells were treated with metformin, and Sonic hedgehog (Shh) mRNA and protein levels were examined by real time reverse transcription-polymerase chain reaction, immunohistochemistry and immunoblotting, respectively. The effect of metformin on Shh levels was also examined in three other cancer cell lines.
  
  
  RESULTS
  Shh protein and mRNA expression was suppressed by metformin in BxPC3 cells. This phenomenon was further confirmed in three other cancer cell lines. Shh mRNA expression was inhibited by metformin in a concentration-dependent manner in two cancer cell lines.
  
  
  CONCLUSIONS
  Metformin reduces the expression of Shh in several cancer cell lines including pancreatic cancer cell.
authors.affiliation: Department of Digestive Surgery, Kawasaki Medical School, 577 Matsushima, Kurashiki, 701-0192, Japan. mnakamura@med.kawasaki-m.ac.jp.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Ayako
authors.initials: A
authors.lastname: Ogo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yamura
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakashima
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008687:Metformin / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D012333:RNA, Messenger; D008687:Metformin
keywords: Hedgehog signaling pathway; Pancreatic cancer; Sonic Hedgehog; metformin