基于 UPLC-Q-TOF-MS 的非靶向血浆代谢组学研究揭示了佩珀罗明 E 在前列腺癌裸鼠模型中的作用。

IF 0.7 4区 医学 Q4 PHARMACOLOGY & PHARMACY Pakistan journal of pharmaceutical sciences Pub Date : 2024-09-01
Shanshan Ma, Shuaishuai Wang, Yunzhi Li
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引用次数: 0

摘要

百部天麻是中国的一种抗癌药用植物,富含一系列新型仲木素,其中包括百部天麻素 E(PE)。在我们之前的研究中,我们证实了 PCa DU145 细胞异种移植肿瘤小鼠模型经 PE 治疗后,体内肿瘤重量和体积显著减少。然而,PE 对 PCa 代谢的影响仍不清楚。因此,本研究的目的是在 PCa 小鼠模型中研究 PE 对代谢调节的影响。本研究基于主成分分析(PCA)、偏最小二乘判别分析(PLS-DA)、潜在生物标记物的鉴定和通路分析,采用非靶向 UPLC-Q-TOF-MS 血浆代谢组学方法探讨了 PE 在人类前列腺癌 DU145 细胞异种移植肿瘤小鼠模型中的作用机制。在裸鼠模型中总共鉴定出 71 个潜在的血浆代谢物生物标志物,其中 36 个在使用 PE 治疗后发生了不同程度的逆转。这些已确定的生物标志物主要与氨基酸代谢、脂肪酸代谢和胆酸代谢有关。这些发现表明,PE 可以改善 DU145 细胞异种移植肿瘤小鼠模型的内源性代谢,为设计治疗 PCa 的新药提供了可靠的基础。
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An untargeted UPLC-Q-TOF-MS-based plasma metabonomics revealed the effects of peperomin E in a prostate cancer nude mouse model.

Peperomia dindygulensis is used as an anticancer medicinal plant in China and is rich in a series of novel secolignans, including peperomin E (PE). In our prior study, we demonstrated the significant reduction in tumor weight and volume in vivo in a PCa DU145 cell xenograft tumor mouse model following PE treatment. However, the impact of PE on PCa metabolism remains unclear. Therefore, the objective of this investigation is to examine the influence of PE on metabolism regulation within a PCa mouse model. An untargeted UPLC-Q-TOF-MS plasma metabolomics approach was carried out to explore the mechanism of action of PE in a human prostate cancer DU145 cell xenograft tumour mouse model based on principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), identification of potential biomarkers and pathway analysis. A total of 71 potential plasma metabolite biomarkers were identified in the nude mouse model and 36 of which were reversed to different degrees after the treatment with PE. These identified biomarkers primarily relate to amino acid metabolism, fatty acid metabolism and cholic acid metabolism. These findings showed that PE could improve endogenous metabolism in the DU145 cell xenograft tumor mouse model and offered a reliable foundation for the design of new therapeutic drugs for treating PCa.

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来源期刊
CiteScore
1.40
自引率
12.50%
发文量
211
审稿时长
4.5 months
期刊介绍: Pakistan Journal of Pharmaceutical Sciences (PJPS) is a peer reviewed multi-disciplinary pharmaceutical sciences journal. The PJPS had its origin in 1988 from the Faculty of Pharmacy, University of Karachi as a biannual journal, frequency converted as quarterly in 2005, and now PJPS is being published as bi-monthly from January 2013. PJPS covers Biological, Pharmaceutical and Medicinal Research (Drug Delivery, Pharmacy Management, Molecular Biology, Biochemical, Pharmacology, Pharmacokinetics, Phytochemical, Bio-analytical, Therapeutics, Biotechnology and research on nano particles.
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