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基于细胞代谢谱的姜黄素对癌细胞的作用机制研究

[Mechanism research of curcumin on cancer cells based on cell metabolic profiling].

作者信息

Hu Jia-Hui, Xu Pan-Pan, Hou Li-Juan, Liu Min, Wang Hua, Gao Guang-Hui, Sun Li-Xin

机构信息

School of Pharmacy, Shenyang Pharmaceutical University Benxi 117004, China.

School of Traditional Chinese Medicine, Shenyang Pharmaceutical University Benxi 117004, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2019 Jun;44(11):2359-2366. doi: 10.19540/j.cnki.cjcmm.20190121.001.

Abstract

In this study, gas chromatography coupled with mass spectrometry(GC-MS) was used to analyze the changes of 12 kinds of cancer cells treated by curcumin. The related differential metabolites were screened and the metabolic pathways were analyzed to explore the anti-tumor mechanism of curcumin. Methyl thiazol tetrazolium(MTT) assay was used to detect the 50% inhibiting concentration(IC_(50)) of curcumin on 12 human tumor cells. After treatment with curcumin for 48 h, the cells were collected and analyzed by GC-MS, followed by pathway analysis and multivariate data analysis including principal component analysis(PCA), orthogonal partial least squares discriminant analysis(OPLS-DA) and One-way analysis of variance(ANOVA),etc. Overall, 34 metabolites showed significant concentration changes after intervention for 48 h, mainly involving multiple metabolic pathways, including lysine degradation, glycine, serine and threonine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, aminoacyl-tRNA biosynthesis, primary bile acid biosynthesis, lysine biosynthesis. In this study, the anti-tumor mechanisms of curcumin interfering with energy metabolism, amino acid metabolism, microtubule system, protein synthesis and oxidative stress response of tumor cells were analyzed from the perspective of metabolism, providing a new reference for further tumor pharmacology study.

摘要

在本研究中,采用气相色谱-质谱联用(GC-MS)技术分析姜黄素处理的12种癌细胞的变化。筛选相关差异代谢物并分析代谢途径,以探究姜黄素的抗肿瘤机制。采用甲基噻唑四氮唑蓝(MTT)法检测姜黄素对12种人肿瘤细胞的半数抑制浓度(IC₅₀)。用姜黄素处理细胞48小时后,收集细胞并进行GC-MS分析,随后进行途径分析和多元数据分析,包括主成分分析(PCA)、正交偏最小二乘判别分析(OPLS-DA)和单因素方差分析(ANOVA)等。总体而言,干预48小时后,34种代谢物的浓度出现显著变化,主要涉及多个代谢途径,包括赖氨酸降解、甘氨酸、丝氨酸和苏氨酸代谢、精氨酸和脯氨酸代谢、半胱氨酸和蛋氨酸代谢、氨酰-tRNA生物合成、初级胆汁酸生物合成、赖氨酸生物合成。本研究从代谢角度分析了姜黄素干扰肿瘤细胞能量代谢、氨基酸代谢、微管系统、蛋白质合成和氧化应激反应的抗肿瘤机制,为进一步的肿瘤药理学研究提供了新的参考。

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