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基于气相色谱-质谱联用的细胞代谢组学研究隐丹参酮对人A2780卵巢癌细胞系的干预机制

Study on the Intervention Mechanism of Cryptotanshinone on Human A2780 Ovarian Cancer Cell Line Using GC-MS-Based Cellular Metabolomics.

作者信息

Wang Tong, Yin Shusheng, Gu Juan, Li Jingjing, Zhang Mengmeng, Shan Jinjun, Wu Xiao, Li Yongming

机构信息

School of Medicine and Holistic Integrative Medicine, Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, Nanjing 210023, China.

Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Medical Metabolomics Center, Nanjing University of Chinese Medicine, Nanjing 210023, China.

出版信息

Pharmaceuticals (Basel). 2023 Jun 9;16(6):861. doi: 10.3390/ph16060861.

Abstract

Cryptotanshinone (CT), an active component of the traditional Chinese medicine Bunge, exhibits a wide range of biological and pharmacological activities. Although the anticancer activity of CT is well known, the knowledge of its effect on the regulation of cancer cell metabolism is relatively new. The present study investigated the anticancer mechanism of CT in ovarian cancer with a focus on cancer metabolism. CCK8 assays, apoptosis assays, and cell cycle assays were conducted to reveal the growth-suppressive effect of CT on ovarian cancer A2780 cells. To explore the potential underlying mechanisms of CT, the changes in endogenous metabolites in A2780 cells before and after CT intervention were investigated using the gas chromatography-mass spectrometry (GC-MS) approach. A total of 28 important potential biomarkers underwent significant changes, mainly involving aminoacyl-tRNA biosynthesis, energy metabolism, and other pathways. Changes in the ATP and amino acid contents were verified with in vitro and in vivo experiments. Our results indicate that CT may exert an anti-ovarian cancer effect by inhibiting ATP production, promoting the protein catabolic process, and inhibiting protein synthesis, which may lead to cell cycle arrest and apoptosis.

摘要

隐丹参酮(CT)是传统中药丹参的一种活性成分,具有广泛的生物学和药理活性。尽管CT的抗癌活性已广为人知,但其对癌细胞代谢调控作用的认识相对较新。本研究以癌症代谢为重点,探讨CT在卵巢癌中的抗癌机制。进行了CCK8检测、凋亡检测和细胞周期检测,以揭示CT对卵巢癌A2780细胞的生长抑制作用。为探究CT潜在的作用机制,采用气相色谱-质谱联用(GC-MS)方法研究了CT干预前后A2780细胞内源性代谢物的变化。共有28种重要的潜在生物标志物发生了显著变化,主要涉及氨酰-tRNA生物合成、能量代谢等途径。通过体外和体内实验验证了ATP和氨基酸含量的变化。我们的结果表明,CT可能通过抑制ATP生成、促进蛋白质分解过程和抑制蛋白质合成来发挥抗卵巢癌作用,这可能导致细胞周期停滞和凋亡。

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