Jeon, J. Y.Lee, M.Whang, S. H.Kim, Jung-whanCho, A.Yun, M.2018-10-222018-10-222018-01-192018-10-220965-0407http://hdl.handle.net/10735.1/6234Altered energy metabolism is a biochemical fingerprint of cancer cells. Hepatocellular carcinoma (HCC) shows reciprocal [¹⁸F]fluorodeoxyglucose (FDG) and [¹¹C]acetate uptake, as revealed by positron emission tomography/computed tomography (PET/CT). Previous studies have focused on the role of FDG uptake in cancer cells. In this study, we evaluated the mechanism and roles of [¹¹C]acetate uptake in human HCCs and cell lines. The expression of monocarboxylate transporters (MCTs) was assessed to determine the transporters of [¹¹C]acetate uptake in HCC cell lines and human HCCs with different [¹¹C]acetate uptake. Using two representative cell lines with widely different [¹¹C]acetate uptake (HepG2 for high uptake and Hep3B for low uptake), changes in [¹¹C]acetate uptake were measured after treatment with an MCT1 inhibitor or MCT1- targeted siRNA. To verify the roles of MCT1 in cells, oxygen consumption rate and the amount of lipid synthesis were measured. HepG2 cells with high [¹¹C]acetate uptake showed higher MCT1 expression than other HCC cell lines with low [¹¹C]acetate uptake. MCT1 expression was elevated in human HCCs with high [¹¹C] acetate uptake compared to those with low [¹¹C]acetate uptake. After blocking MCT1 with AR-C155858 or MCT1 knockdown, [¹¹C]acetate uptake in HepG2 cells was significantly reduced. Additionally, inhibition of MCT1 suppressed mitochondrial oxidative phosphorylation, lipid synthesis, and cellular proliferation in HCC cells with high [¹¹C]acetate uptake. MCT1 may be a new therapeutic target for acetate-dependent HCCs with high [¹¹C]acetate uptake, which can be selected by [¹¹C]acetate PET/CT imaging in clinical practice.en"Oncology Research is an open access journal and follows rules governed by open access publications."©2018 Cognizant, LLCCarcinoma, HepatocellularMonocarboxylic Acid TransportersPositron-Emission TomographyAcetic acidSmall interfering RNACell proliferationGene Knockdown TechniquesGene targetingHumansLipogenesisOxygen consumption (Physiology)PhosphorylationLiver--CancerTomography, EmissionOxygen ConsumptionarticleJeon, J. Y., M. Lee, S. H. Whang, J. -W Kim, et al. 2018. "Regulation of acetate utilization by Monocarboxylate Transporter 1 (MCT1) in Hepatocellular Carcinoma (HCC)." Oncology Research 26(1), doi: 10.3727/096504017X14902648894463261