Metformin suppressed the proliferation of LoVo cells and induced a time-dependent metabolic and transcriptional alteration.
Metformin suppressed the proliferation of LoVo cells and induced a time-dependent metabolic and transcriptional alteration.
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DOI：
10.1038/srep17423
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发表时间：
2015-11-30
影响因子：
4.6
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
He J;Wang K;Zheng N;Qiu Y;Xie G;Su M;Jia W;Li H
二甲双胍是一种应用广泛的抗糖尿病药物，具有潜在的抗肿瘤活性。然而，人们对其对肿瘤细胞的整体代谢和转录影响知之甚少。在目前的研究中，我们对10 mM二甲双胍处理8、24和48小时的人源性结肠癌LoVo细胞进行了代谢分析。在细胞活力降低之前，从8到48小时观察到明显的时间依赖性代谢改变。在对照组和二甲双胍处理的细胞之间，在三个时间点共鉴定出47、45和66种差异代谢物。大多数代谢产物在8 h时被二甲双胍上调，而在24和48 h时被二甲双胍下调。这些代谢物主要参与碳水化合物、脂类、氨基酸、维生素和核苷酸的代谢途径。同时，在二甲双胍作用8和24 h时，转录组分析显示有134和3061个差异表达基因。除了肿瘤信号通路外，细胞能量代谢通路相关基因的表达也发生了显著改变，这一点在糖代谢通路相关基因中得到了进一步验证。总之，我们目前的数据表明，二甲双胍抑制LoVo细胞的增殖，这可能是由于在代谢和转录水平上以一种时间依赖性的方式调节细胞能量代谢。
Metformin is a widely used anti-diabetic drug with potential anti-tumor activity. However, little is known about its global metabolic and transcriptional impacts on tumor cells. In current study, we performed a metabolic profiling on human-derived colon cancer LoVo cells treated by 10 mM metformin for 8, 24 and 48 h. An obvious time-dependent metabolic alteration was observed from 8 to 48 h, prior to the reduction of cell viability. A total of 47, 45 and 66 differential metabolites were identified between control and metformin-treated cells at three time points. Most of the metabolites were up-regulated at 8 h, but down-regulated at 24 and 48 h by metformin. These metabolites were mainly involved in carbohydrates, lipids, amino acids, vitamins and nucleotides metabolism pathways. Meanwhile, the transcirptomic profile revealed 134 and 3061 differentially expressed genes at 8 and 24 h by metformin. In addition to the cancer signaling pathways, expression of genes involved in cell energy metabolism pathways was significantly altered, which were further validated with genes in glucose metabolism pathway. Altogether, our current data indicate that metformin suppressed the proliferation of LoVo cells, which may be due to the modulation on cell energy metabolism at both metabolic and transcriptional levels in a time-dependent way.