title: Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth.
abstract: BACKGROUND
  The most common genetic changes identified in human NSCLC are Kras mutations (10-30 %) and p53 mutation or loss (50-70 %). Moreover, NSCLC with mutations in Kras and p53 poorly respond to current therapies, so we are trying to find a new target for the treatment strategies.
  
  
  METHODS
  Flow cytometry, crystal violet staining and immunoblotting were used to assess cell cycle arrest, proliferation and apoptosis in lung cancer cell lines after 2-DG treatment and lentivirus infection by shRNA knock down. IHC and western blotting were carried for NSG xenograft model with 2-DG treatment and lentivirus infection by shRNA knock down.
  
  
  RESULTS
  Knocking down Kras down-regulated the glycolytic enzyme hexokinase II (HK2) in KP2 (mouse lung cancer cell line with Kras mutation and p53 deletion) and H23 (human lung cancer cell line with Kras mutation and p53 mutation) cell lines. Genetic studies revealed that HK2 was required for the human and mouse lung cancer cell growth in vitro and in vivo. Our pharmacological studies confirmed that 2-DG, an inhibitor of HK2, inhibited human and mouse lung cancer cell growth through inducing cell apoptosis and autophagy.
  
  
  CONCLUSIONS
  HK2 is a promising treatment target for NSCLC with Kras activating and p53 function loss.
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193 China ; Laboratory of Cancer Genetics, The University of Minnesota Hormel Institute, Austin, MN 55912 USA.
authors.forename: Huanan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Laboratory of Cancer Genetics, The University of Minnesota Hormel Institute, Austin, MN 55912 USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Laboratory of Cancer Genetics, The University of Minnesota Hormel Institute, Austin, MN 55912 USA.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Laboratory of Cancer Genetics, The University of Minnesota Hormel Institute, Austin, MN 55912 USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory of Cancer Genetics, The University of Minnesota Hormel Institute, Austin, MN 55912 USA.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Deng
authors.affiliation: The Clinical Department, College of Veterinary Medicine, China Agricultural University, Beijing, 100193 China.
authors.forename: Degui
authors.initials: D
authors.lastname: Lin
keywords: 2-DG; Apoptosis; HK2; Kras; NSCLC