Inhibition of glycolytic enzyme hexokinase II HK2 suppresses lung tumor growthReport as inadecuate




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Cancer Cell International

, 16:9

First Online: 16 February 2016Received: 01 July 2015Accepted: 03 February 2016

Abstract

BackgroundThe 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.

MethodsFlow 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.

ResultsKnocking 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.

ConclusionsHK2 is a promising treatment target for NSCLC with Kras activating and p53 function loss.

KeywordsNSCLC HK2 Kras 2-DG Apoptosis An erratum to this article can be found at http:-dx.doi.org-10.1186-s12935-016-0313-6.

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Author: Huanan Wang - Lei Wang - Yingjie Zhang - Ji Wang - Yibin Deng - Degui Lin

Source: https://link.springer.com/article/10.1186/s12935-016-0280-y







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