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糖酵解途径及糖酵解相关基因在人类结直肠癌发生中的意义

Significance of the glycolytic pathway and glycolysis related-genes in tumorigenesis of human colorectal cancers.

作者信息

Yeh Ching-Sheng, Wang Jaw-Yuan, Chung Fu-Yen, Lee Su-Chen, Huang Ming-Yii, Kuo Chia-Wei, Yang Ming-Je, Lin Shiu-Ru

机构信息

Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan, ROC.

出版信息

Oncol Rep. 2008 Jan;19(1):81-91.

Abstract

We investigated gene expressions involved in the glycolytic pathways in colorectal cancer. The study was designed to use gene ontology and its relevant bioinformatics tools to analyze the microarray data obtained from CRC tissues and their corresponding normal tissues, in order to explore the correlation between the glycolytic metabolic pathway and possible pathogenesis of this disease. The overexpression of glycolysis-related genes was observed in over 76% of CRC tissues. In addition, we stimulated the SW480 and SW620 CRC cell lines with 15 mM D-(+)-glucose and 10 mM 2-deoxy-D-glucose respectively. The results indicate that the proliferation response of both the SW480 and SW620 cell lines increased remarkably with a time-dependent effect by D-(+)-glucose administration. In contrast, the proliferation response of both the SW480 and SW620 cell lines was significantly inhibited by 2-DG administration. Likewise, further analyses of the expression of related genes triggered by the D-(+)-glucose in vivo show that the activation process of these eight genes - GLUT1, HK1, GPI, GAPD, PGK1, PGK2, ENO2, PKM2 - prominently increased with a time-dependent effect. In conclusion, this study demonstrates that the glycolytic pathway and glycolysis-related genes may play an important role in the tumorigenesis of CRC, but their molecular mechanisms need further investigation to verify this.

摘要

我们研究了大肠癌糖酵解途径中涉及的基因表达。本研究旨在利用基因本体及其相关生物信息学工具分析从结直肠癌组织及其相应正常组织获得的微阵列数据,以探讨糖酵解代谢途径与该疾病可能的发病机制之间的相关性。在超过76%的结直肠癌组织中观察到糖酵解相关基因的过表达。此外,我们分别用15 mM D-(+)-葡萄糖和10 mM 2-脱氧-D-葡萄糖刺激SW480和SW620结直肠癌细胞系。结果表明,给予D-(+)-葡萄糖后,SW480和SW620细胞系的增殖反应均随时间依赖性显著增加。相反,给予2-DG可显著抑制SW480和SW620细胞系的增殖反应。同样,对体内D-(+)-葡萄糖引发的相关基因表达的进一步分析表明,这八个基因——GLUT1、HK1、GPI、GAPD、PGK1、PGK2、ENO2、PKM2——的激活过程随时间依赖性显著增加。总之,本研究表明糖酵解途径和糖酵解相关基因可能在结直肠癌的肿瘤发生中起重要作用,但其分子机制需要进一步研究以证实这一点。

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