Laboratories of Veterinary Radiotherapy, Nihon University College of Bioresource Sciences, Kameino, Fujisawa, Kanagawa, Japan.
Laboratory for Cellular Function Conversion Technology, RIKEN Center for Integrative Medical Sciences, Suehiro-cho, Tsurumi, Yokohama, Kanagawa, Japan.
PLoS One. 2021 Feb 4;16(2):e0243859. doi: 10.1371/journal.pone.0243859. eCollection 2021.
The rate of glucose uptake dramatically increases in cancer cells even in the presence of oxygen and fully functioning mitochondria. Cancer cells produce ATP by glycolysis rather than oxidative phosphorylation under aerobic conditions, a process termed as the "Warburg effect." In the present study, we treated canine melanoma cells with the glucose analog 2-deoxy-D-glucose (2-DG) and investigated its effect on cell growth. 2-DG attenuated cell growth in a time- and dose-dependent manner. Cell growth was also inhibited following treatment with the glucose transporter (GLUT) inhibitor WZB-117. The treatment of 2-DG and WZB-117 attenuated the glucose consumption, lactate secretion and glucose uptake of the cells. The mRNA expression of the subtypes of GLUT was examined and GLUT1 and GLUT3 were found to be expressed in melanoma cells. The growth, glucose consumption and lactate secretion of melanoma cells transfected with siRNAs of specific for GLUT1 and GLUT3 was suppressed. These findings suggest that glucose uptake via GLUT1 and GLUT3 plays a crucial role for the growth of canine melanoma cells.
即使在氧气存在和功能完整的线粒体的情况下，癌细胞中的葡萄糖摄取率也会大幅增加。在有氧条件下，癌细胞通过糖酵解而不是氧化磷酸化产生 ATP，这一过程被称为“Warburg 效应”。在本研究中，我们用葡萄糖类似物 2-脱氧-D-葡萄糖（2-DG）处理犬黑色素瘤细胞，并研究其对细胞生长的影响。2-DG 以时间和剂量依赖的方式减弱细胞生长。用葡萄糖转运蛋白（GLUT）抑制剂 WZB-117 处理后，细胞生长也受到抑制。2-DG 和 WZB-117 的处理减弱了细胞的葡萄糖消耗、乳酸分泌和葡萄糖摄取。检查了 GLUT 亚型的 mRNA 表达，发现黑色素瘤细胞中表达 GLUT1 和 GLUT3。转染了针对 GLUT1 和 GLUT3 的特异性 siRNA 的黑色素瘤细胞的生长、葡萄糖消耗和乳酸分泌受到抑制。这些发现表明，通过 GLUT1 和 GLUT3 的葡萄糖摄取对犬黑色素瘤细胞的生长起着至关重要的作用。
