Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado Anschutz Medical Campus, Mail Stop 8106, Aurora, CO 80045, USA.
Department of Biochemistry and Molecular Genetics, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Cells. 2023 May 12;12(10):1374. doi: 10.3390/cells12101374.
Thyroid cancer is the most common endocrine neoplasm, and despite its overall high survival rate, patients with metastatic disease or tumors that resist radioactive iodine experience a significantly worse prognosis. Helping these patients requires a better understanding of how therapeutics alter cellular function. Here, we describe the change in metabolite profiles after treating thyroid cancer cells with the kinase inhibitors dasatinib and trametinib. We reveal alterations to glycolysis, the TCA cycle, and amino acid levels. We also highlight how these drugs promote short-term accumulation of the tumor-suppressive metabolite 2-oxoglutarate, and demonstrate that it reduces the viability of thyroid cancer cells in vitro. These results show that kinase inhibition profoundly alters the metabolome of cancer cells and highlight the need to better understand how therapeutics reprogram metabolic processes, and ultimately, cancer cell behavior.
甲状腺癌是最常见的内分泌肿瘤，尽管总体存活率较高，但患有转移性疾病或对放射性碘有抵抗的肿瘤的患者预后明显较差。要帮助这些患者，就需要更好地了解治疗方法如何改变细胞功能。在这里，我们描述了用激酶抑制剂达沙替尼和曲美替尼处理甲状腺癌细胞后代谢物谱的变化。我们揭示了糖酵解、三羧酸循环和氨基酸水平的改变。我们还强调了这些药物如何促进肿瘤抑制代谢物 2-氧戊二酸的短期积累，并证明它降低了甲状腺癌细胞在体外的活力。这些结果表明，激酶抑制会深刻改变癌细胞的代谢组，并强调需要更好地了解治疗方法如何重新编程代谢过程，最终改变癌细胞的行为。
