胰岛素和油酸促进结肠癌皮下移植瘤生长的代谢组学研究
Metabolomic study on the effects of insulin and oleic acid on the development of colon cancer xenografts
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摘要: 为探讨胰岛素及油酸对结肠癌血清代谢物的调节作用，建立结肠癌细胞HCT116皮下移植瘤模型。裸鼠随机分为4组，每组6只，分别为对照组（CON）、胰岛素组（INS，每日皮下注射胰岛素2.5 U/kg）、油酸组（OA，每日灌胃油酸2.0 g/kg）、胰岛素及油酸联合给药组（IO，每日皮下注射胰岛素2.5 U/kg、灌胃油酸2.0 g/kg）。采用气质联用（GC/MS）及液质联用（LC-IT-TOF/MS）技术对各组血清样本进行非目标代谢组学分析。数据经前处理如峰识别、去卷积和峰对齐后，导入SIMCA-P软件进行多元统计分析。结果表明，IO组裸鼠体重最轻但瘤体最重，且IO组与CON组相比，血清代谢轮廓发生显著变化，主要差异代谢物为尿素、阿拉伯糖、胆固醇、L-乙酰肉碱和鞘氨醇；OA及INS组与对照组之间无明显差异。本研究表明，胰岛素和油酸联合给药促进了结肠癌发展，扰动了代谢物轮廓，研究结果可为结肠癌生物标志物发现及早期诊断提供理论依据。Abstract: To investigate the regulatory effects of insulin and oleic acid on serum metabolites in colon cancer, subcutaneous transplantation tumor model of colon carcinoma cell HCT116 was established. Nude mice were randomly divided into 4 groups: control (CON, vehicle); insulin treatment (INS, sc, 2.5 U/kg); oleic acid treatment (OA, ig, 2.0 g/kg); and insulin (sc, 2.5 U/kg) plus oleic acid (ig, 2.0 g/kg) treatment (IO). Non-target metabolomic analysis on the blood samples was performed by GC/MS and LC-IT-TOF/MS. Data pre-processing, including peaking, spectral deconvolution and peak alignment, was performed before data were imported to SIMCA-P for multivariate statistical analysis. Results showed that body weight of individuals in IO group was the lowest, but the tumor weight was the heaviest. Metabolic profiles of IO group were also different compared with the CON group, and the contributing metabolites were urea, arabinose, cholesterol, L-acetylcarnitine and sphingosine. There was no significant difference between OA or INS and CON. This study showed that the combination of insulin and oleic acid promoted colon cancer deterioration and caused metabolic disturbance in blood.Our study may provide theoretical foundation for the discovery of colon cancer biomarker and its early diagnosis.
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Keywords:
- insulin /
- oleic acid /
- colon cancer /
- metabolomics
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