The combination of the glycolysis inhibitor 2-DG and sorafenib can be effective against sorafenib-tolerant persister cancer cells

OncoTargets and Therapy
Li WangXiaoxia Liu

Abstract

Chemotherapy remains a major clinical option for the successful treatment of cancer by eliminating fast-growing populations of cancer cells. However, drug resistance causes the failure of antitumor treatment. Increasing evidence suggests that a small subpopulation of cancer cells will enter a "persister state" under drug pressure. The persister cell pool constitutes a reservoir from which drug resistance may emerge. Therefore, targeting persister cells presents a therapeutic opportunity to prevent drug resistance and impede tumor relapse. RT-qPCR, Western blot, Seahorse, apoptosis assay, clonogenic assay, and xenografted mouse model were used for this study. We showed that a similar therapy-resistant cell state underlies the behavior of persister cells derived from sorafenib treatments with reversible, nonmutational mechanisms. Then, we demonstrated that persister cells showed upregulated glycolysis, as evidenced by higher ECAR, as well as increased glucose consumption and lactate production. A database analysis showed that sorafenib-tolerant persister cells exhibited the increased expression of the glycolytic enzyme hexokinase 2, which is closely related to the poor prognosis in liver cancer. We found that the combined treatme...Continue Reading

Citations

Sep 26, 2019·Chembiochem : a European Journal of Chemical Biology·Elena S Reckzeh, Herbert Waldmann
Apr 23, 2020·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Yan QianWei Song
Jul 8, 2020·Journal of Experimental & Clinical Cancer Research : CR·Jiao FengChuanyong Guo
Oct 9, 2020·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Pegah FarhadiKamran Mansouri
Oct 24, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jiaqi LiAndrea L A Wong
Jun 9, 2021·Genes and Environment : the Official Journal of the Japanese Environmental Mutagen Society·Amir Sadra Zangouei, Meysam Moghbeli
Aug 31, 2021·The Journal of Biological Chemistry·Cameron A SchmidtP Darrell Neufer
Nov 14, 2020·Cell·Shensi ShenCaroline Robert

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Datasets Mentioned

BETA
GSE10186

Methods Mentioned

BETA
PCR
Protein Assay
flow cytometry
Biosensor
Assay
xenograft
xenografts

Software Mentioned

CellQuest Pro
SPSS Statistics
Prism GraphPad
ImageJ

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