title: Propofol induces apoptosis and increases gemcitabine sensitivity in pancreatic cancer cells in vitro by inhibition of nuclear factor-κB activity.
abstract: OBJECTIVE
  To investigate the effect of propofol on human pancreatic cells and the molecular mechanism of propofol action.
  
  
  METHODS
  We used the human pancreatic cancer cell line MIAPaCa-2 for in vitro studies measuring growth inhibition and degree of apoptotic cell death induced by propofol alone, gemcitabine alone, or propofol followed by gemcitabine. All experiments were conducted in triplicate and carried out on three or more separate occasions. Data were means of the three or more independent experiments ± SE. Statistically significant differences were determined by two-tailed unpaired Student's t test and defined as P < 0.05.
  
  
  RESULTS
  Pretreatment of cells with propofol for 24 h followed by gemcitabine resulted in 24%-75% growth inhibition compared with 6%-18% when gemcitabine was used alone. Overall growth inhibition was directly correlated with apoptotic cell death. We also showed that propofol potentiated gemcitabine-induced killing by downregulation of nuclear factor-κB (NF-κB). In contrast, NF-κB was upregulated when pancreatic cancer cells were exposed to gemcitabine alone, suggesting a potential mechanism of acquired chemoresistance.
  
  
  CONCLUSIONS
  Inactivation of the NF-κB signaling pathway by propofol might abrogate gemcitabine-induced activation of NF-κB, resulting in chemosensitization of pancreatic tumors to gemcitabine.
authors.affiliation: Qi-Hang Du, Yan-Bing Xu, Meng-Yuan Zhang, Peng Yun, Chang-Yao He, Department of Anesthesiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China.
authors.forename: Qi-Hang
authors.initials: QH
authors.lastname: Du
authors.forename: Yan-Bing
authors.initials: YB
authors.lastname: Xu
authors.forename: Meng-Yuan
authors.initials: MY
authors.lastname: Zhang
authors.forename: Peng
authors.initials: P
authors.lastname: Yun
authors.forename: Chang-Yao
authors.initials: CY
authors.lastname: He
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D015742:Propofol / Q000008:administration & dosage*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D006993:Hypnotics and Sedatives; D016328:NF-kappa B; D003841:Deoxycytidine; D015742:Propofol; D000093542:Gemcitabine
keywords: Apoptosis; Gemcitabine; Nuclear factor-κB; Pancreatic cancer; Propofol
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