Neeman M, Degani H
Isotope Department, Weizmann Institute of Science, Rehovot, Israel.
Cancer Res. 1989 Feb 1;49(3):589-94.
The effects of 17 beta-estradiol treatment versus tamoxifen on the metabolism of human breast cancer T47D-clone 11 cells were studied by noninvasive 31P and 13C nuclear magnetic resonance techniques. 31P nuclear magnetic resonance spectra revealed differences between estrogen and tamoxifen treated cells. The steady state content of phosphorylcholine and of the nucleoside diphosphates was higher in the tamoxifen treated cells by 33 and 140%, respectively, relative to estrogen treated cells. The intracellular pH of 7.2 and the content of the nucleoside triphosphates, Pi, phosphocreatine, glycerolphosphorylcholine, and glycerolphosphorylethanolamine and uridine diphosphoglucose remained the same in both treatments. Glucose utilization and subsequent lactate, glutamate, alanine, and glycerol 3-phosphate synthesis were monitored on line following administration of specifically labeled [13C]glucose. In estrogen treated cells the rate of lactate production via glycolysis was 560 fmol/cell/h and the initial rate of 13C labeling of the glutamate pool via the Krebs cycle was 6.8 fmol/cell/h. In the tamoxifen treated cells these rates were 2-fold lower, at 250 and 2.9 fmol/cell/h for lactate and glutamate labeling, respectively. In estrogen treated cells, the calculated content of glutamate (19 fmol/cell), alanine (11 fmol/cell), and glycerol 3-phosphate (8 fmol/cell) was higher than in tamoxifen treated cells, where only glutamate labeling was detected (13 fmol/cell). The observed differences in the in vivo kinetics of glucose metabolism may provide a sensitive measure for detecting the response of human breast cancer cells to estrogen versus tamoxifen treatments.
采用非侵入性的³¹P和¹³C核磁共振技术，研究了17β-雌二醇治疗与他莫昔芬对人乳腺癌T47D克隆11细胞代谢的影响。³¹P核磁共振谱显示了雌激素和他莫昔芬处理细胞之间的差异。相对于雌激素处理的细胞，他莫昔芬处理的细胞中磷酸胆碱和核苷二磷酸的稳态含量分别高出33%和140%。两种处理中细胞内pH值为7.2，三磷酸核苷、无机磷、磷酸肌酸、甘油磷酸胆碱、甘油磷酸乙醇胺和尿苷二磷酸葡萄糖的含量保持不变。在给予特异性标记的[¹³C]葡萄糖后，在线监测葡萄糖利用及随后的乳酸、谷氨酸、丙氨酸和3-磷酸甘油的合成。在雌激素处理的细胞中，通过糖酵解产生乳酸的速率为560 fmol/细胞/小时，通过三羧酸循环对谷氨酸池的¹³C标记初始速率为6.8 fmol/细胞/小时。在他莫昔芬处理的细胞中，这些速率分别降低了2倍，乳酸和谷氨酸标记速率分别为250和2.9 fmol/细胞/小时。在雌激素处理的细胞中，计算得出的谷氨酸（19 fmol/细胞）、丙氨酸（11 fmol/细胞）和3-磷酸甘油（8 fmol/细胞）的含量高于他莫昔芬处理的细胞，后者仅检测到谷氨酸标记（13 fmol/细胞）。观察到的葡萄糖代谢体内动力学差异可能为检测人乳腺癌细胞对雌激素与他莫昔芬治疗的反应提供一种灵敏的方法。
