Breast cancer cells MCF-7 and MDA-MB-231 were treated with Tamoxifen (5 μM) or Paclitaxel (1 μM) or with a combination of the two drugs. Herein, we have employed gas chromatography coupled with mass spectroscopy to identify metabolic changes occurring as response to different drug treatments. We report the identification of sixty-one metabolites and overall the two studied cell lines showed a distinct metabolomic profile from each other. Further data analysis indicates that a total of 30 metabolites were significantly differentially abundant in MCF-7 drug-treated cells, most of the metabolic changes occurred when cells were treated with either Tamoxifen (15) or Paclitaxel (25). On the other side, a total of 31 metabolites were significantly differentially abundant in MDA-MB-31 cells with drug treatment. Similarly, to MCF-7 most of the metabolic changes occurred when cells were treated with either Tamoxifen (19) or Paclitaxel (20). In conclusion, this report demonstrates that Tamoxifen and/or Paclitaxel treatment have a pronounced effect on the main metabolic pathways in both breast cancer (BC) cell lines (MCF-7 and MDA-MB231), which could be used as a foundation for future investigations to understand the possible effect of these drugs on different metabolic pathways.

Significance

Metabolic profiling of cancer cells is a promising tool in tumor diagnosis, biomarker discovery and drug treatment protocols, since cancer cells exhibit altered metabolism when compared to normal cells. Although numerous studies have reported the use of various OMICs applications to investigate breast cancer cells, very few of these have performed thorough screening of metabolites in such cells. Our investigation highlights the first study to characterize MCF7 and MDA-MB-231 cancer cells treated with Tamoxifen and/or Paclitaxel and to identify the affected metabolic pathways. Such findings might play an important role in revealing the molecular bases of the underlying mechanism of action of these two frontline anti-breast cancer drugs.

中文翻译：

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用他莫昔芬和/或紫杉醇处理的MCF-7和MDA-MB-231癌细胞的基于GC-MS的比较代谢组学分析。

乳腺癌细胞MCF-7和MDA-MB-231用他莫昔芬（5μM）或紫杉醇（1μM）或两种药物联合治疗。在本文中，我们采用了气相色谱法和质谱法相结合的方法来鉴定代谢变化，这是对不同药物治疗的反应。我们报告了六十一种代谢物的鉴定，总体而言，这两种研究的细胞系显示出彼此不同的代谢组学特征。进一步的数据分析表明，在MCF-7药物处理的细胞中共有30种代谢物显着差异丰富，大多数代谢变化发生在用他莫昔芬（15）或紫杉醇（25）处理细胞时。另一方面，经药物处理后，MDA-MB-31细胞中共有31种代谢物显着差异丰富。同样，当使用Tamoxifen（19）或Paclitaxel（20）处理细胞时，MCF-7的大部分代谢发生。总之，该报告表明，他莫昔芬和/或紫杉醇治疗对两种乳腺癌（BC）细胞系（MCF-7和MDA-MB231）的主要代谢途径均具有显着影响，可作为将来的基础调查以了解这些药物对不同代谢途径的可能作用。

意义

癌细胞的代谢谱分析是肿瘤诊断，生物标志物发现和药物治疗方案中的有前途的工具，因为与正常细胞相比，癌细胞的代谢发生了改变。尽管许多研究已经报道了使用各种OMIC应用来研究乳腺癌细胞，但是很少有这种药物能够对这类细胞中的代谢物进行彻底的筛选。我们的研究突出了第一项研究，该研究表征了用他莫昔芬和/或紫杉醇治疗的MCF7和MDA-MB-231癌细胞的特征，并确定了受影响的代谢途径。这些发现可能在揭示这两种一线抗乳腺癌药物的潜在作用机制的分子基础中起重要作用。