结肠癌不同转移潜能细胞株SW620及SW480的代谢组学研究

Metabonomics analysis of colorectal carcinoma cell lines SW480 and SW620 with different metastatic potentials

目的:分析不同转移潜能结肠癌细胞株的代谢模式,筛选并探讨差异代谢物与结肠癌转移的关系。方法:利用~1H NMR技术,采用PLS-DA模型分析高转移潜能SW620和低转移潜能SW480细胞株的代谢模式,并定量差异表达代谢物。利用Seahorse能量代谢仪分析,进一步探讨代谢能力。结果:不同转移潜能的2株结肠癌细胞的代谢模式能够在第一主成分上明显分开。与原发灶结肠癌细胞SW480相比,具有高转移潜能的SW620细胞中乳酸、琥珀酸、异亮氨酸、丙氨酸、甘氨酸水平较高(P<0.05),乙酸、氧化磷酸胆碱、ATP、肌苷和牛磺酸水平较低(P<0.05)。转移潜能高的SW620细胞具有更高的糖酵解水平、TCA循环活性、细胞外酸化率和线粒体耗氧率水平。结论:不同转移潜能结肠癌细胞株SW480/SW620的代谢模式具有显著差异,与SW480细胞相比,SW620具有较高的代谢基础潜能,提示其高转移能力的能量需要,也能更快适应其所在微环境,证明转移过程的发生与代谢密切相关。

Objective:To study the metabolic profiles of human colorectal carcinoma cell lines with different metastatic potentials and analyze the relationship between metabolites and the metastasis of colorectal carcinomas.Methods:The characteristic alterations in metabolites of two isogenic colorectal cancer cell lines(highly metastatic SW620 and nonmetastatic SW480)were explored by the PLS-DA model based on the 1H NMR spectra.Moreover,Seahorse XF analyzer was used to assess ECAR and OCR.Results:The metabolic profile of SW620 and SW480 cell lines displayed obvious differences along in the PC1 direction.Compared with SW480,lactate,succinic,isoleucine,acetate,glycine and glutamine were increased,and phosphorylcholine,ATP,inositol and taurine were reduced in SW620 cells(P<0.05).SW620 cells with high metastatic potential have higher levels of glycolysis,TCA cycle activity,ECAR and OCR levels.Conclusion:The metabolic profile of SW620 cells with high metastatic potential shows clear differences from SW480 cells,and a variety of metabolites can be involved in the metastasis of colorectal carcinoma.Compared with SW480 cells,SW620 has a higher metabolic base potential,suggesting that it needs energy for high metastatic ability.Meanwhile,SW620 can adapt to its microenvironment more quickly,suggesting that the occurrence of metastasis is closely related to metabolism.