Metabolomics reveals the effect of valproic acid on MCF-7 and MDA-MB-231 cells

1. Breast cancer is one of the most common malignancies in women worldwide. Metabolomics has been shown to be a promising strategy to elucidate the underlying pathogenesis of cancer and identify new targets for cancer diagnosis and therapy. Valproic acid (VPA), a histone deacetylase inhibitor, is a potential new drug in tumor therapy. This work used metabolomics to examine the effect of VPA on metabolism in breast cancer cells. 2. Based on UPLC-MS/MS, we identified 3137 differential metabolites in human breast cancer MCF-7 cells and 2472 differential metabolites in human breast cancer MDA-MB-231 cells after VPA treatment. 3. We selected 63 differential metabolites from MCF-7 samples and 61 differential metabolites from MDA-MB-231 cells with the more conspicuous changing trend. Furfural was up-regulated after VPA treatment in both cell lines. In both samples, VPA exerted an effect on the beta-alanine metabolism pathway and the taurine and hypotaurine metabolism pathway. 4. This study identified the effect of VPA on metabolites and metabolic pathways in breast cancer cells, and these findings may contribute to the identification of new targets for breast cancer treatment.

1. 乳腺癌是全球女性最常见的恶性肿瘤之一。代谢组学（metabolomics）已被证实是阐明癌症潜在发病机制、发掘癌症诊断与治疗新靶点的极具前景的策略。丙戊酸（Valproic acid, VPA）作为一种组蛋白去乙酰化酶抑制剂，是肿瘤治疗领域颇具潜力的新型药物。本研究借助代谢组学技术，探究了丙戊酸对乳腺癌细胞代谢的影响。
2. 本研究基于超高效液相色谱-串联质谱（UPLC-MS/MS）技术，在经丙戊酸处理的人乳腺癌MCF-7细胞中鉴定出3137种差异代谢物，在人乳腺癌MDA-MB-231细胞中鉴定出2472种差异代谢物。
3. 我们从MCF-7细胞样本中筛选出63种变化趋势更为显著的差异代谢物，从MDA-MB-231细胞中筛选出61种此类差异代谢物。在两种细胞系中，呋喃甲醛（Furfural）经丙戊酸处理后均呈现上调表达。在两类样本中，丙戊酸均可对β-丙氨酸代谢通路以及牛磺酸与次牛磺酸代谢通路产生调控作用。
4. 本研究明确了丙戊酸对乳腺癌细胞代谢物及代谢通路的调控作用，相关发现可为乳腺癌治疗新靶点的发掘提供参考依据。