title: Inhibition of SIRT1 combined with gemcitabine therapy for pancreatic carcinoma.
abstract: BACKGROUND
  Pancreatic carcinoma possesses one of the highest lethality rates, highest drug-resistance, and highest incidence rates. The objective of this research was to enhance the efficacy and drug-resistance for pancreatic carcinoma by using inhibition of SIRT1 combined with gemcitabine therapy methods.
  
  
  METHODS
  Three pancreatic carcinoma cells (PANC-1 cells, BxPC-3 cells, and SW1990 cells) received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vitro; then BxPC-3 pancreatic cancer xenogeneic mice also received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo.
  
  
  RESULTS
  The cleaved poly ADP ribose polymerase (PARP)-1 effect of drug in pancreatic carcinoma cells was significantly different (P < 0.05) and the efficacy in descending order was the combination therapy with inhibition of SIRT1 and gemcitabine, inhibition of SIRT1, and gemcitabine. The BxPC-3 pancreatic cancer xenogeneic mice model received treatment with physiological saline, inhibition of SIRT1, gemcitabine, and combination therapy with inhibition of SIRT1 and gemcitabine in vivo and the results showed that the tumor volumes decreased and the survival rate within 45 days increased according to the order of the given drugs and the difference was significant (P < 0.05).
  
  
  CONCLUSIONS
  Combination therapy with inhibition of SIRT1 and gemcitabine could improve efficacy and survival time in a BxPC-3 pancreatic cancer xenogeneic mice model, compared with single inhibition of SIRT1, or single gemcitabine therapy. The combination therapy method is a potential treatment method for pancreatic carcinoma.
authors.affiliation: Department of Hepatobiliary-Pancreatic Surgery, Jinhua Hospital of Zhejiang University, Jinhua, People's Republic of China.
authors.forename: Dao-Jun
authors.initials: DJ
authors.lastname: Gong
authors.forename: Jia-Min
authors.initials: JM
authors.lastname: Zhang
authors.forename: Min
authors.initials: M
authors.lastname: Yu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhuang
authors.forename: Qing-Qu
authors.initials: QQ
authors.lastname: Guo
mesh_terms: D000818:Animals; D017209:Apoptosis; D001549:Benzamides / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D004591:Electrophoresis, Polyacrylamide Gel; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D009284:Naphthols / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D056564:Sirtuin 1; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D001549:Benzamides; D009284:Naphthols; C439060:sirtinol; D003841:Deoxycytidine; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000093542:Gemcitabine
keywords: combination therapy; inhibition of SIRT1-gemcitabine; pancreatic carcinoma
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