Targeting glycolysis with 2-deoxy-D-glucose sensitizes primary cell cultures of renal cell carcinoma to tyrosine kinase inhibitors

Journal of Cancer Research and Clinical Oncology
Adrian Georg SimonMarieta Ioana Toma

Abstract

To investigate the synergistic effect of glycolysis inhibition on therapy answer to tyrosine kinase inhibitors in renal carcinoma. Primary cell cultures from 33 renal tumors including clear cell RCC (ccRCC), papillary RCC and the rare subtype chromophobe RCC as well as two metastases of ccRCC were obtained and cultivated. The patient-derived cells were verified by immunohistochemistry. CcRCC cells were further examined by exon sequencing of the von Hippel-Lindau gene (VHL) and by RNA-sequencing. Next, cell cultures of all subtypes of RCC were exposed to increasing doses of various tyrosine kinase inhibitors (axitinib, cabozantinib and pazopanib) and the glycolysis inhibitor 2-deoxy-D-glucose, alone or combined. CellTiter-Glo® Luminescence assay and Crystal Violet staining were used to assess the inhibition of glycolysis and the viability of the cultured primary cells. The cells expressed characteristic tissue markers and, in case of ccRCC cultures, the VHL status of the tumor they derived from. An upregulation of HK1, PFKP and SLC2A1 was observed, while components of the respiratory chain were downregulated, confirming a metabolic shift towards aerobic glycolysis. The tumors displayed variable individual responses for the thera...Continue Reading

References

Jan 12, 2007·The New England Journal of Medicine·Robert J MotzerRobert A Figlin
Jun 10, 2009·Bioinformatics·Heng LiUNKNOWN 1000 Genome Project Data Processing Subgroup
Jun 19, 2012·Seminars in Cancer Biology·W Marston Linehan, Christopher J Ricketts
Jan 17, 2013·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Cora N SternbergIan D Davis
Apr 5, 2013·Anti-cancer Drugs·Sebastiano ButiFrancesco Massari
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Jan 8, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Ramaprasad SrinivasanW Marston Linehan
Jan 27, 2015·European Urology·Borje LjungbergAxel Bex
Mar 10, 2015·Nature Methods·Daehwan KimSteven L Salzberg
Aug 22, 2016·Urologic Oncology·Ilya Tsimafeyeu
Jun 6, 2017·Biochimica Et Biophysica Acta. General Subjects·Mariana MoraisRui Medeiros
Aug 2, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Krzysztof M KrawczykMartin E Johansson
Feb 22, 2018·Advances in Anatomic Pathology·Mohammed AkhtarTurki Al Hussain
Mar 22, 2018·The New England Journal of Medicine·Robert J MotzerUNKNOWN CheckMate 214 Investigators
May 24, 2018·Current Topics in Medicinal Chemistry·Nicholas S AkinsHoang V Le
Sep 24, 2018·European Urology·Umberto CapitanioPaul Russo
Oct 30, 2018·Nucleic Acids Research·John G TateSimon A Forbes
Feb 20, 2019·The New England Journal of Medicine·Robert J MotzerToni K Choueiri
Jun 12, 2019·International Journal of Urology : Official Journal of the Japanese Urological Association·Keiichi Ito
Aug 25, 2019·Cancers·Javier C Angulo, Oleg Shapiro

❮ Previous
Next ❯

Citations

Apr 9, 2021·Nature Reviews. Nephrology·Paulo José BassoNiels Olsen Saraiva Câmara

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.