18F-FDG PET/CT for Monitoring the Response of Breast Cancer to miR-143-Based Therapeutics by Targeting Tumor Glycolysis

Autor: Ying Miao, Ling-fei Zhang, Rui Guo, Sheng Liang, Min Zhang, Shuo Shi, Cheng-fang Shang-Guan, Mo-fang Liu, Biao Li
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: Molecular Therapy: Nucleic Acids, Vol 5, Iss C (2016)
Druh dokumentu: article
ISSN: 2162-2531
DOI: 10.1038/mtna.2016.72
Popis: Increased glucose utilization is a hallmark of cancer, and tumor metabolism is emerging as anticancer target for therapeutic intervention. Triple-negative breast cancers TNBC are highly glycolytic and show poor clinical outcomes. We previously identified hexokinase 2, the major glycolytic enzyme, as a target gene of miR-143 in TNBC. Here, we developed a therapeutic formulation using cholesterol-modified miR-143 agomir encapsulated in a neutral lipid-based delivery agent that blocked tumor growth and glucose metabolism in TNBC tumor-bearing mice when administered systemically. The antioncogenic effects were accompanied by a reduction in the direct target hexokinase 2 and [18F]-fluorodeoxyglucose (18F-FDG) uptake based on positron emission tomography/computed tomography. Treatment with miR-143 formulation has minimal toxic effects and mice tolerated it well. Thus, we demonstrated that miR-143 is a robust inhibitor of the Warburg effect and an effective therapeutic target for TNBC. In addition, 18F-FDG positron emission tomography/computed tomography can be used to specifically monitor the response of TNBC to miR-143-based therapeutics by targeting tumor glycolysis.
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