Huang Chun-Yin, Weng Yu-Ting, Li Po-Chen, Hsieh Nien-Tsu, Li Chun-I, Liu Hsiao-Sheng, Lee Ming-Fen
Department of Nutrition, China Medical University, Taichung 406040, Taiwan.
Department of Nutrition and Health Sciences, Chang Jung Christian University, Tainan 711301, Taiwan.
Life (Basel). 2021 Sep 14;11(9):963. doi: 10.3390/life11090963.
Increasing lines of evidence indicate that the biologically active form of vitamin D, calcitriol (1,25-dihydroxyvitamin D), prevents cancer progression by reducing cell proliferation, increasing cell differentiation, and inhibiting angiogenesis, among other potential roles. Cancer cells in solid tumors preferably undergo the "Warburg effect" to support cell growth by upregulating glycolysis, and the glycolytic intermediates further serve as building blocks to generate biomass. The objective of the current study is to investigate whether calcitriol affects glucose metabolism and cell growth in human colorectal cancer cells. Calcitriol reduced the expression of cyclin D1 and c-Myc. In addition, calcitriol reduced the expression of glucose transporter 1 (GLUT1) and key glycolytic enzymes and decreased extracellular acidification rate but increased oxygen consumption rate in human colorectal cancer cells. In a subcutaneous HT29 xenograft NOD/SCID mouse model, the volume and weight of the tumors were smaller in the calcitriol groups as compared with the control group, and the expression levels of GLUT1 and glycolytic enzymes, hexokinase 2 and lactate dehydrogenase A, were also lower in the calcitriol groups in a dose-responsive manner. Our data indicate that calcitriol suppresses glycolysis and cell growth in human colorectal cancer cells, suggesting an inhibitory role of the biologically active form of vitamin D in colorectal cancer progression.
越来越多的证据表明，维生素D的生物活性形式骨化三醇（1,25-二羟基维生素D）通过减少细胞增殖、增加细胞分化以及抑制血管生成等潜在作用来阻止癌症进展。实体瘤中的癌细胞更倾向于通过上调糖酵解来经历“瓦伯格效应”以支持细胞生长，并且糖酵解中间产物进一步作为生成生物量的原料。本研究的目的是调查骨化三醇是否会影响人结肠癌细胞中的葡萄糖代谢和细胞生长。骨化三醇降低了细胞周期蛋白D1和c-Myc的表达。此外，骨化三醇降低了人结肠癌细胞中葡萄糖转运蛋白1（GLUT1）和关键糖酵解酶的表达，降低了细胞外酸化率，但增加了氧消耗率。在皮下HT29异种移植NOD/SCID小鼠模型中，与对照组相比，骨化三醇组的肿瘤体积和重量更小，并且骨化三醇组中GLUT1和糖酵解酶己糖激酶2和乳酸脱氢酶A的表达水平也呈剂量依赖性降低。我们的数据表明，骨化三醇抑制人结肠癌细胞中的糖酵解和细胞生长，提示维生素D的生物活性形式在结肠癌进展中具有抑制作用。
