Combined 18F-FDG PET/CT imaging and a gastric orthotopic xenograft model in nude mice are used to evaluate the efficacy of glycolysis-targeted therapy

• Published in: Oncology reports Vol. 39; no. 1; pp. 271 - 279
• Main Authors: Wang, Ting-An, Xian, Shu-Lin, Guo, Xing-Yu, Zhang, Xiao-Dong, Lu, Yun-Fei
• Format: Journal Article
• Language: English
• Published: Greece Spandidos Publications UK Ltd 01.01.2018
• Subjects: Animals; Apoptosis; Cancer therapies; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Citrates - administration & dosage; Citrates - pharmacology; Female; Fluorodeoxyglucose F18 - metabolism; Gastric cancer; Gene Expression Regulation, Neoplastic - drug effects; Glycolysis - drug effects; Humans; Injections, Intraperitoneal; Mice; Mice, Nude; Positron Emission Tomography Computed Tomography - methods; Pyruvates - administration & dosage; Pyruvates - pharmacology; Random Allocation; Stomach Neoplasms - diagnostic imaging; Stomach Neoplasms - drug therapy; Stomach Neoplasms - metabolism; Studies; Treatment Outcome; Tumors; Xenograft Model Antitumor Assays; United States > US; China; Japan
• ISSN: 1021-335X; 1791-2431
• DOI: 10.3892/or.2017.6060

As discovered by Warburg 80 years ago most malignant cells rely more on glycolysis than normal cells. The high rate of glycolysis provides faster ATP production and greater lactic acid for tumor proliferation and invasion, thus indicating a potential target in anticancer therapy. Our previous studies demonstrated that 3-bromopyruvate (3-BrPA) and sodium citrate (SCT) inhibited tumor cell proliferation in vitro. However, the underlying mechanisms still warrant further investigation. In the present study, we employed the human SGC-7901 gastric cancer cell line, built an orthotopic xenograft model in nude mice, examined the treatment response by 18F-FDG PET/CT and investigated the mechanisms of 3-BrPA and SCT in vivo. Our results demonstrated that glycolysis and tumor growth were inhibited by intraperitoneal injection of 3-BrPA and SCT, which were imaged using an 18F-FDG PET/CT scanner. In addition, apoptosis induced by 3-BrPA and SCT was initiated by the upregulation of Bax and downregulation of Bcl-2, which promote cytochrome c release and subsequently activate caspase-9 and -3, and ultimately execute mitochondria-mediated apoptosis. Furthermore, apoptosis was also modulated by the generation of ROS and inhibition of survivin. Accordingly, 3-BrPA and SCT can inhibit glycolysis and induce gastric cancer apoptosis through the mitochondrial caspase-dependent pathway.