Cell Metabolomics Reveals the Potential Mechanism of Aloe Emodin and Emodin Inhibiting Breast Cancer Metastasis.
Cell Metabolomics Reveals the Potential Mechanism of Aloe Emodin and Emodin Inhibiting Breast Cancer Metastasis.
复制标题
细胞代谢组学揭示芦荟大黄素和大黄素抑制乳腺癌转移的潜在机制
DOI：
10.3390/ijms232213738
复制
发表时间：
2022-11-08
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
转移是影响乳腺癌治疗和预后的主要障碍之一。本研究通过细胞代谢组学研究芦荟大黄素（AE）和大黄素（EMD）抑制乳腺癌转移的作用及其可能机制。首先，建立MCF-7与HUVEC细胞共培养模型，并与传统的MCF-7细胞单培养进行比较。结果表明，HUVEC细胞可促进癌细胞向恶性表型发展。在共培养模型中，AE和EMD均能抑制MCF-7细胞的粘附、侵袭和血管生成，并诱导细胞凋亡。然后，采用基于UPLC-Q-TOF/MS多元统计分析的代谢组学方法探讨AE和EMD抑制MCF-7细胞转移的潜在机制。因此，AE组和EMD组分别鉴定出27个和13个生物标志物，包括多胺代谢、蛋氨酸循环、TCA循环、谷胱甘肽代谢、嘌呤代谢和天冬氨酸合成。对典型代谢物进行定量分析，结果显示AE的抑制效果明显优于EMD。这些结果证实AE和EMD可以通过不同途径抑制乳腺癌细胞的转移。我们的研究提供了AE和EMD对抗乳腺癌转移的潜在机制的整体视图。
Metastasis is one of the main obstacles for the treatment and prognosis of breast cancer. In this study, the effects and possible mechanisms of aloe emodin (AE) and emodin (EMD) for inhibiting breast cancer metastasis were investigated via cell metabolomics. First, a co-culture model of MCF-7 and HUVEC cells was established and compared with a traditional single culture of MCF-7 cells. The results showed that HUVEC cells could promote the development of cancer cells to a malignant phenotype. Moreover, AE and EMD could inhibit adhesion, invasion, and angiogenesis and induce anoikis of MCF-7 cells in co-culture model. Then, the potential mechanisms behind AE and EMD inhibition of MCF-7 cell metastasis were explored using a metabolomics method based on UPLC-Q-TOF/MS multivariate statistical analysis. Consequently, 27 and 13 biomarkers were identified in AE and EMD groups, respectively, including polyamine metabolism, methionine cycle, TCA cycle, glutathione metabolism, purine metabolism, and aspartate synthesis. The typical metabolites were quantitatively analyzed, and the results showed that the inhibitory effect of AE was significantly better than EMD. All results confirmed that AE and EMD could inhibit metastasis of breast cancer cells through different pathways. Our study provides an overall view of the underlying mechanisms of AE and EMD against breast cancer metastasis.