title: Expression of heat shock protein 70 modulates the chemoresponsiveness of pancreatic cancer.
abstract: OBJECTIVE
  Heat shock protein (HSP) 70 is constitutively overexpressed in pancreatic cancer cells (PCCs) and appears to confer protection against chemotherapeutics. We investigated whether modulating HSP 70 increases chemoresponsiveness to gemcitabine in PCCs.
  
  
  METHODS
  Varying concentrations of quercetin and gemcitabine, either alone or in combination, were added to PCCs (Panc-1 and MiaPaCa-2). MTT assay was performed to analyze cell viability. HSP 70 expression was assessed by Western blot analysis. Apoptosis was determined by measuring caspase-3 activity. Western blot for the LC3-II protein detected the presence of autophagy.
  
  
  RESULTS
  HSP 70 levels were not affected by the incubation of Panc-1 and MiaPaCa-2 cells with gemcitabine, whereas with quercetin, the levels were reduced in both cell lines. The viability of both Panc-1 and MiaPaCa-2 cells significantly decreased with gemcitabine treatment but not with quercetin. A combination of gemcitabine and quercetin decreased the viability of both cell lines in a dose-dependent manner, which was more pronounced than gemcitabine treatment alone. Treatment with either gemcitabine or quercetin augmented caspase-3 activity in both cell lines, and a combination of these compounds further potentiated caspase-3 activity. LC3-II protein expression was negligible with gemcitabine treatment but marked with quercetin. The addition of gemcitabine to quercetin did not potentiate LC3-II protein expression.
  
  
  CONCLUSIONS
  Modulation of HSP 70 expression with quercetin enhanced the chemoresponsiveness of PCCs to gemcitabine. The mechanism of cell death was both apoptosis and autophagy.
authors: Division of Gastroenterology and Hepatology, Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
authors: Jong Jin
authors: JJ
authors: Hyun
authors: Hong Sik
authors: HS
authors: Lee
authors: Bora
authors: B
authors: Keum
authors: Yeon Seok
authors: YS
authors: Seo
authors: Yoon Tae
authors: YT
authors: Jeen
authors: Hoon Jai
authors: HJ
authors: Chun
authors: Soon Ho
authors: SH
authors: Um
authors: Chang Duck
authors: CD
authors: Kim
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011794:Quercetin / Q000494:pharmacology; D000093542:Gemcitabine
chemical_list: D018840:HSP70 Heat-Shock Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D003841:Deoxycytidine; D011794:Quercetin; D053148:Caspase 3; D000093542:Gemcitabine
keywords: Gemcitabine; Heat shock proteins; Pancreatic neoplasms; Quercetin