Semenza Gregg L
Vascular Program, Institute for Cell Engineering, Department of Pediatrics, John Hopkins University School of Medicine, Baltimore, Maryland, USA.
J Clin Invest. 2008 Dec;118(12):3835-7. doi: 10.1172/JCI37373. Epub 2008 Nov 20.
Tumors contain well-oxygenated (aerobic) and poorly oxygenated (hypoxic) regions, which were thought to utilize glucose for oxidative and glycolytic metabolism, respectively. In this issue of the JCI, Sonveaux et al. show that human cancer cells cultured under hypoxic conditions convert glucose to lactate and extrude it, whereas aerobic cancer cells take up lactate via monocarboxylate transporter 1 (MCT1) and utilize it for oxidative phosphorylation (see the related article beginning on page 3930). When MCT1 is inhibited, aerobic cancer cells take up glucose rather than lactate, and hypoxic cancer cells die due to glucose deprivation. Treatment of tumor-bearing mice with an inhibitor of MCT1 retarded tumor growth. MCT1 expression was detected exclusively in nonhypoxic regions of human cancer biopsy samples, and in combination, these data suggest that MCT1 inhibition holds potential as a novel cancer therapy.
肿瘤包含富氧（有氧）区域和低氧（缺氧）区域，人们认为这两种区域分别利用葡萄糖进行氧化代谢和糖酵解代谢。在本期《临床研究杂志》中，松沃等人表明，在缺氧条件下培养的人类癌细胞将葡萄糖转化为乳酸并排出，而有氧癌细胞则通过单羧酸转运蛋白1（MCT1）摄取乳酸并将其用于氧化磷酸化（见第3930页开始的相关文章）。当MCT1受到抑制时，有氧癌细胞摄取葡萄糖而非乳酸，而缺氧癌细胞则因葡萄糖剥夺而死亡。用MCT1抑制剂治疗荷瘤小鼠可延缓肿瘤生长。在人类癌症活检样本的非缺氧区域专门检测到了MCT1的表达，综合这些数据表明，抑制MCT1具有作为一种新型癌症治疗方法的潜力。
