Abstract
Cancer cells alter regular metabolic pathways in order to sustain rapid proliferation. One example of metabolic remodeling in cancerous tissue is the upregulation of pyruvate kinase isoenzyme M2 (PKM2), which is involved in aerobic glycolysis. Indeed, PKM2 has previously been identified as a tumor biomarker and as a potential target for cancer therapy. Here, the role of PKM2 in the anticancer efficacy of 5-fluorouracil (5-FU) was evaluated in colorectal cancer (CRC). HCT116, SW480 and HT-29 cells were used by transfection with lentiviral vectors expressing short hairpin RNA (shRNA) against PKM2. In response to 5-FU treatment, cellular proliferation was examined, the levels of ATP/ADP ratio were monitored, the intracellular accumulation of 5-FU was measured, and intracellular levels of phosphoenolpyruvate (PEP), pyruvate and lactate were evaluated by using liquid chromatography-mass spectrometry (LC-MS). A CRC subcutaneous tumor model was performed to investigate the effect of PKM2 inhibition on 5-FU efficacy in vivo. Suppression of PKM2 resulted in changes in glucose metabolism, leading to decreased synthesis of adenosine triphosphate (ATP). Reduced levels of ATP/ADP ratio resulted in the intracellular accumulation of 5-FU, con...Continue Reading
References
Apr 29, 2000·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·G J PetersH M Pinedo
Feb 15, 2001·Current Medicinal Chemistry·A Garnier-SuillerotW Priebe
Mar 21, 2002·Nature Reviews. Cancer·Michael M GottesmanSusan E Bates
Mar 14, 2008·Nature·Heather R ChristofkLewis C Cantley
Mar 14, 2008·Nature·Heather R ChristofkLewis C Cantley
Jan 13, 2012·CA: a Cancer Journal for Clinicians·Rebecca SiegelAhmedin Jemal
Oct 16, 2012·Nature·Barbara ChanetonEyal Gottlieb
Dec 18, 2012·Nature·Oliver D K MaddocksKaren H Vousden
Dec 26, 2012·Proceedings of the National Academy of Sciences of the United States of America·Marta Cortés-CrosFrancesco Hofmann
Jul 16, 2013·Nature Cell Biology·Georgia VelimeziVassilis G Gorgoulis
Jun 6, 2014·Cell Biochemistry and Biophysics·Jinxia HeHoujie Liang
Sep 27, 2015·Cancer Chemotherapy and Pharmacology·Linna ZhangPeter E Zage
Oct 31, 2015·Journal of Cancer·Yang LinLi Fu
Apr 14, 2016·Updates in Surgery·Pasqualino FavoritiFrancesco Corcione
May 25, 2016·Cancer Chemotherapy and Pharmacology·James J LeeEdward Chu
Aug 31, 2016·International Journal of Oncology·Fang LiangWei Xiong
Dec 31, 2016·Cell Research·Ji LiangWeiwei Yang
May 26, 2017·Journal of Cellular Biochemistry·Xiao-Ling YanLin Guan
Jul 27, 2017·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Ran AoJia-Ni Wang
Citations
Jul 4, 2019·Nutrition and Cancer·Gang WangKe Xu
Jan 30, 2021·Molecular and Cellular Biochemistry·Zhi YuYingying Tang
Dec 10, 2020·Cancer Cell International·Xun ChenDongsheng Yu
Mar 17, 2021·Journal of Experimental & Clinical Cancer Research : CR·Chuan-Yi HuJi-Dong Xu