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Cancer Cell International
Published in: Cancer Cell International 1/2016

Open Access 01-12-2016 | Primary research

Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth

Authors: Huanan Wang, Lei Wang, Yingjie Zhang, Ji Wang, Yibin Deng, Degui Lin

Published in: Cancer Cell International | Issue 1/2016

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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.
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Metadata
Title
Inhibition of glycolytic enzyme hexokinase II (HK2) suppresses lung tumor growth
Authors
Huanan Wang
Lei Wang
Yingjie Zhang
Ji Wang
Yibin Deng
Degui Lin
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2016
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-016-0280-y

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