Department of Gastrointestinal and Pediatric Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan.
Surg Today. 2012 May;42(5):460-9. doi: 10.1007/s00595-011-0027-2. Epub 2011 Nov 11.
Most cancer cells exhibit increased glycolysis. The elevated glucose transporter 1 (GLUT1) expression has been reported to be associated with resistance to therapeutic agents and a poor prognosis. We wondered whether GLUT1 expression was associated with the clinical outcome in rectal cancer after preoperative chemoradiotherapy (CRT), and whether glycolysis inhibition could represent a novel anticancer treatment.
We obtained total RNA from residual cancer cells using microdissection from a total of 52 rectal cancer specimens from patients who underwent preoperative CRT. We performed transcriptional analyzes, and studied the association of the GLUT1 gene expression levels with the clinical outcomes. In addition, we examined each proliferative response of three selected colorectal cancer cell lines to a glycolysis inhibitor, 3-bromopyruvic acid (3-BrPA), with regard to their expression of the GLUT1 gene.
An elevated GLUT1 gene expression was associated with a high postoperative stage, the presence of lymph node metastasis, and distant recurrence. Moreover, elevated GLUT1 gene expression independently predicted both the recurrence-free and overall survival. In the in vitro studies, we observed that 3-BrPA significantly suppressed the proliferation of colon cancer cells with high GLUT1 gene expression, compared with those with low expression.
An elevated GLUT1 expression may be a useful predictor of distant recurrence and poor prognosis in rectal cancer patients after preoperative CRT.
大多数癌细胞表现出增强的糖酵解。据报道，葡萄糖转运蛋白 1（GLUT1）的高表达与对治疗药物的耐药性和不良预后相关。我们想知道 GLUT1 表达是否与术前放化疗（CRT）后直肠癌的临床结果相关，以及糖酵解抑制是否可以代表一种新的抗癌治疗方法。
我们从接受术前 CRT 的 52 例直肠癌患者的总共 52 个直肠癌标本中使用显微切割获得残留癌细胞的总 RNA。我们进行了转录分析，并研究了 GLUT1 基因表达水平与临床结果的关联。此外，我们检查了三种选定的结直肠癌细胞系中每个对糖酵解抑制剂 3-溴丙酮酸（3-BrPA）的增殖反应，关于它们的 GLUT1 基因表达。
升高的 GLUT1 基因表达与术后高分期、淋巴结转移和远处复发有关。此外，升高的 GLUT1 基因表达独立预测了无复发生存和总生存。在体外研究中，我们观察到与低表达的细胞相比，3-BrPA 显著抑制了高 GLUT1 基因表达的结肠癌细胞的增殖。
在术前 CRT 后，升高的 GLUT1 表达可能是直肠癌患者远处复发和不良预后的有用预测指标。
