title: Transforming growth factor beta receptor I inhibitor sensitizes drug-resistant pancreatic cancer cells to gemcitabine.
abstract: BACKGROUND
  Resistance to gemcitabine is a major obstacle in the treatment of advanced pancreatic cancer. Previous exploration of protein kinase inhibitors demonstrated that blocking transforming growth factor-β (TGFβ) signal enhances the efficacy of gemcitabine in pancreatic cancer cells.
  
  
  METHODS
  We analyzed the cell viability after combinational treatment of TGFβ receptor I (TβRI) inhibitors, SB431542 and SB525334 with gemcitabine in pancreatic cancer cells. In addition, apoptotic cell death and cell migration were measured.
  
  
  RESULTS
  Combination with TβRI inhibitors significantly augmented the cytotoxicity of gemcitabine in both parental and gemcitabine resistant pancreatic cancer cells. SB525334 significantly increased apoptotic cell death in gemcitabine-resistant cells. Treatment of SB525334 also affected the AKT signalling pathway, which plays a crucial role in gemcitabine resistance. Migration assay also revealed that blocking TβRI reduces cell migration.
  
  
  CONCLUSIONS
  Chemotherapeutic approaches using SB525334 might enhance the treatment benefit of the gemcitabine-containing regimens in the treatment of pancreatic cancer patients.
authors.affiliation: WCU Research Center of Nanobiomedical Science, Dankook University, San 29, Anseo-Dong, Cheonan 330-714, Korea.
authors.forename: Yeon Jeong
authors.initials: YJ
authors.lastname: Kim
authors.forename: Jae Seok
authors.initials: JS
authors.lastname: Hwang
authors.forename: Young Bin
authors.initials: YB
authors.lastname: Hong
authors.forename: Insoo
authors.initials: I
authors.lastname: Bae
authors.forename: Yeon-Sun
authors.initials: YS
authors.lastname: Seong
mesh_terms: D000964:Antimetabolites, Antineoplastic; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011810:Quinoxalines / Q000494:pharmacology*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors*; D000093542:Gemcitabine
chemical_list: C521813:6-(2-tert-butyl-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline; D000964:Antimetabolites, Antineoplastic; D007093:Imidazoles; D011810:Quinoxalines; D018125:Receptors, Transforming Growth Factor beta; D003841:Deoxycytidine; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D000093542:Gemcitabine