title: [Inhibition of Sirolimus on the growth of pancreatic carcinoma and its effect on the expression of glucose transporter and hexokinase Ⅱ].
abstract: OBJECTIVE
  To investigate whether Sirolimus could affect the glycolytic catabolism pathways of pancreatic carcinoma through the control of hypoxia induced factor (HIF-1α) to inhibit the growth of tumor, and explore the potential mechanism of targeting the signaling pathways of mTOR for the treatment of pancreatic carcinoma.
  
  
  METHODS
  Sirolimus was applied to treat the pancreatic carcinoma in nude mice orthotopic transplantation model, its difference with the control group was compared; RT-PCR and Western blot were used to measure the mRNA and protein expression of mTOR, HIF-1α, Glucose carrier protein 1 (GLUT-1) and Hexokinase Ⅱ (HK-Ⅱ), respectively; the changes of activity of HK-Ⅱ in the tumor was determined.
  
  
  RESULTS
  The tumor mass of the control group (1.97±0.21)g was significantly larger than that of the Sirolimus group (0.38±0.10)g (P<0.01), and the volume of the control group (1.40±0.15) mm(3) was significantly larger than that of the Sirolimus group (0.27±0.07) mm(3) (P<0.01). The expressions of mTOR, GLUT-1 and HK-Ⅱ mRNA in the control group were higher than those of the Sirolimus group (P<0.05), while no significant change was observed in the expression of HIF-1α (P>0.05); the expressions of p-mTOR, HIF-1α, GLUT-1 and HK-Ⅱ proteins in the control group were higher than those of the Sirolimus group (P<0.05). The activity of HK-Ⅱ in the control group was higher than that of the Sirolimus group (P<0.05).
  
  
  CONCLUSIONS
  Sirolimus could affect the expression of GLUT-1 and HK-Ⅱ in pancreatic carcinoma through the effects of HIF-1α to inhibit tumor growth, indicating that blocking the mTOR pathway could control the glycolytic metabolism pathways of pancreatic carcinoma, which may become the new strategy for the treatment of pancreatic carcinoma.
authors.affiliation: Department of Pancreatic Surgery, the First Affiliated Hospital of China Medical University, Shenyang 110001, China.
authors.forename: J P
authors.initials: JP
authors.lastname: Huang
authors.forename: J L
authors.initials: JL
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Hua
authors.forename: P
authors.initials: P
authors.lastname: Huang
authors.forename: C L
authors.initials: CL
authors.lastname: Ge
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D051246:Glucose Transport Proteins, Facilitative / Q000187:drug effects*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006593:Hexokinase; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects*; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D012333:RNA, Messenger; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases
chemical_list: D000903:Antibiotics, Antineoplastic; D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; C495677:SLC2A1 protein, human; D006593:Hexokinase; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus