Analysis of metabonomic profiling alterations in a mouse model of colitis-associated cancer and 2-deoxy-d-glucose treatment
Analysis of metabonomic profiling alterations in a mouse model of colitis-associated cancer and 2-deoxy-d-glucose treatment
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DOI：
10.1039/c6ra01718e
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发表时间：
2016-06
期刊：
影响因子：
3.9
通讯作者：
Peng Yang;Li Zongwei;Lichao Zhang;Hanqing Li;Zhuoyu Li
中科院分区：
文献类型：
--
作者：
Peng Yang;Li Zongwei;Lichao Zhang;Hanqing Li;Zhuoyu Li
炎症与结直肠癌（CRC）的发生、发展和肿瘤代谢密切相关。2-脱氧-D-葡萄糖（2-DG）是一种糖酵解抑制剂，具有抗肿瘤活性，被认为是一种很有前途的肿瘤治疗药物。然而，由炎症和2-DG预防引起的肿瘤发生的代谢改变仍然难以捉摸。在这项研究中，气相色谱飞行时间质谱（GC-TOF/MS）分析应用于研究2-DG对氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）诱导的结肠炎相关癌症模型中代谢物的改变的抗癌活性。结果表明，2-DG能明显降低AOM和DSS诱导的小鼠成瘤率。AOM/DSS组中有14种代谢产物显著降低，而2-DG处理后所有这些代谢产物均被逆转。代谢途径分析（MetPA）揭示了亚油酸代谢、磷酸戊糖代谢、烟酸和烟酰胺代谢以及磷酸肌醇代谢等4个代谢网络的参与。亚油酸、烟酰胺、5-磷酸核糖和肌醇的代谢产物在这四条途径中发生了显著变化。此外，2-DG处理减弱AOM和DSS诱导的PKM 2表达。总之，这项研究提供了一个深入了解2-DG如何显示抗癌作用，并可能作为结肠炎相关癌症的治疗剂。
Inflammation is well recognized to be associated with tumorigenesis, cancer progression and tumor metabolism of colorectal cancer (CRC). 2-Deoxy-D-glucose (2-DG), a glycolytic inhibitor, has been reported to possess anticancer properties and is considered to be a promising treatment for tumors. However, the metabolic alteration in tumorigenesis caused by inflammation and 2-DG prevention remains elusive. In this study, a gas chromatography time-of-flight mass spectrometry (GC-TOF/MS) analysis was applied to investigate the anticancer activity of 2-DG on the alteration of metabolites in a colitis-associated cancer model induced by azoxymethane (AOM) and dextran sodium sulfate (DSS). The data showed that 2-DG obviously decreased the incidence of tumor formation induced by AOM and DSS. 14 metabolites were significantly decreased in the AOM/DSS group, while all these metabolites were reversed by 2-DG treatment. Furthermore, metabolic pathway analysis (MetPA) was introduced to reveal the involvement of four metabolic networks including linoleic acid metabolism, pentose phosphate pathway, nicotinate and nicotinamide metabolism and inositol phosphate metabolism. The significantly altered metabolites of linoleic acid, nicotinamide, ribose-5-phosphate and myo-inositol were involved in these four pathways. Moreover, the expression of PKM2, which was induced by AOM and DSS, was attenuated by 2-DG treatment. Together, this study provides an insight into how 2-DG shows anticancer effects and may serve as a therapeutic agent for colitis-associated cancer.