Analysis of Mechanism of Artesunate in Treatment of Liver Cancer Based on Metabolomics

Hui-guo WANG; Si-yao WANG; Xin-long HAN; Yu-tong LI; Li-xia YUAN; Xiao-mei TAN; Qing-fa TANG; Xue-feng XING; Fei-long CHEN; Ya-lei YIN; Ling TANG

doi:10.13422/j.cnki.syfjx.20191548

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Analysis of Mechanism of Artesunate in Treatment of Liver Cancer Based on Metabolomics

Drug Metabolism | 更新时间：2021-02-09

- Analysis of Mechanism of Artesunate in Treatment of Liver Cancer Based on Metabolomics
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 22, Pages: 78-85(2019)
- 作者机构：
  
  1.大连大学　生命科学与技术学院，辽宁　大连　 116622；
  2.中国科学院　大连化学物理研究所中国科学院分离分析化学重点实验室，转化医学科学研究中心，辽宁　大连　 116023；
  3.南方医科大学　中医药学院，广东省中药制剂重点实验室，广东省中药制剂技术工程实验室，广州　 510515
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191548
  CLC： R22; R945; R28; Q2; R969.1; O657
- Received：25 December 2018，
  
  Published Online：09 April 2019，
  
  Published：20 November 2019
- 稿件说明：
移动端阅览
Hui-guo WANG, Si-yao WANG, Xin-long HAN, et al. Analysis of Mechanism of Artesunate in Treatment of Liver Cancer Based on Metabolomics[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(22): 78-85.
DOI：

Hui-guo WANG, Si-yao WANG, Xin-long HAN, et al. Analysis of Mechanism of Artesunate in Treatment of Liver Cancer Based on Metabolomics[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(22): 78-85. DOI： 10.13422/j.cnki.syfjx.20191548.

摘要

目的：

采用GC-MS联用技术探索青蒿琥酯治疗肝癌的作用机制，为该药物在肝癌治疗中的临床应用提供实验依据。

方法：

应用发光法细胞活力检测试剂盒(CellTiter-Glo® Luminescent Cell Viability Assay)检测不同浓度青蒿琥酯(0，12.5，25，50，100 μmol·L

－1

)作用于人肝癌Huh7，SMMC-7721细胞24，48，72 h的活性。采用GC-MS联用技术分析青蒿琥酯作用于2种肝癌细胞(Huh7，SMMC-7721)24 h后代谢物的变化，利用Postrun Analysis 4.41工作站对数据进行预处理，采用偏最小二乘法-判别分析(PLS-DA)对两组差异代谢物进行分析，通过MetaboAnalyst 3.0软件对差异代谢物进行代谢通路分析。

结果：

与正常组相比，青蒿琥酯作用于2种肝癌细胞后，细胞内相同代谢物共有39种发生了显著变化，主要涉及到氨基酰-转运RNA(tRNA)生物合成，丙氨酸、天冬氨酸和谷氨酸代谢，甘氨酸、丝氨酸和苏氨酸代谢，精氨酸和脯氨酸代谢，谷胱甘肽代谢5条代谢通路。

结论：

青蒿琥酯(12.5～100 μmol·L

－1

)均能够抑制肝癌细胞(Huh7，SMMC-7721)的生长，主要涉及到5条代谢通路，这可能是青蒿琥酯抗肝癌的作用途径。

Abstract

Objective:

To study on the antitumor mechanism of artesunate in the treatment of liver cancer based on gas chromatography-mass spectrometry (GC-MS).

Method:

CellTiter-Glo® Luminescent Cell Viability Assay was used to detect activity of artesunate with different concentrations (0

12.5

100 μmol·L

-1

) on human liver cancer Huh7

SMMC-7721 cells for 24

72 h. GC-MS was employed to analyze the changes of metabolites of artesunate in two kinds of hepatoma cells (Huh7

SMMC-7721) for 24 h. The data was preprocessed by Postrun Analysis 4.41 workstation. Partial least squares-discriminant analysis (PLS-DA) was used to analyze two sets of differential metabolites and to analyze metabolic pathways of differential metabolites based on MetaboAnalyst 3.0 software.

Result:

Compared with the normal group

after two kinds of liver cancer cells was treated by artesunate

a total of 39 identical metabolites in the cells have undergone significant changes

which were mainly related to five metabolic pathways

including biosynthesis of aminoacyl-transfer RNA (tRNA)

metabolism of alanine

aspartic acid and glutamic acid

metabolism of glycine

serine and threonine

metabolism of arginine and proline

metabolism of glutathione.

Conclusion:

Artesunate (12.5-100 μmol·L

-1

) can inhibit the growth of liver cancer cells (Huh7

SMMC-7721)

it mainly involves five metabolic pathways

which may be the pathway of artesunate against liver cancer.

关键词

Keywords

references

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