Investigation of Mechanism of Tryptanthrin Inhibiting Breast Cancer in Mice Based on Proteomics
10.13422/j.cnki.syfjx.20201161
- VernacularTitle:基于蛋白质组学分析色胺酮抑制小鼠乳腺癌的作用机制
- Author:
Qing-fang ZENG
1
;
Cai-rong LUO
1
;
Xiao-yan ZHANG
1
;
Yan LIANG
1
;
Xiang-chun SHEN
1
;
Ling TAO
1
;
Wei ZHOU
1
Author Information
1. School of Pharmacy，Key Laboratory of Optimal Utilizaiton of Natural Medicinal Resources， Guizhou Medical University， Guiyang 550025， China
- Publication Type:Research Article
- Keywords:
tryptanthrin;
breast cancer;
4T1 cells;
proteomics;
differentially expressed protein;
tumor inflammatory microenvironment;
pharmacological effects
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2020;26(21):173-180
- CountryChina
- Language:Chinese
-
Abstract:
Objective:A systematical study on the anti-breast cancer mechanism of tryptanthrin in breast cancer-bearing mice was done by Label-free proteomics. Method:UPLC-MS was used to detect the expressed-proteins of tryptanthrin inhibiting breast cancer in mice， chromatographic separation was achieved on the Ionoptics nano UPLC C18 column （0.075 mm×250 mm， 1.6 μm）， and gradient elution was performed with 0.1% formic acid aqueous solution-0.1% formic acid acetonitrile solution as mobile phase. Data acquisition was carried out in electrospray ionization （ESI） under the positive ion mode， the scanning range was m/z 100-1 700， MaxQuant 1.6.5.0 was used for database retrieval. Label-free proteomics with high resolution mass spectrometry was used to screen differentially expressed proteins between the model group of 4T1 breast cancer mice and oral administration group of tryptanthrin （100 mg·kg-1）. The proteomics of tryptanthrin against breast cancer was carried out. Result:A total of 3 997 proteins were identified in this proteomics research， and 2 911 proteins were quantifiable. A total of 750 differentially expressed proteins were identified between the model group and the tryptanthrin group， 286 proteins were up-regulated and 464 proteins were down-regulated. Gene ontology analysis showed that these differentially expressed proteins were mainly involved in biological processes of proliferation， cell migration， apoptosis， immunity， angiogenesis， inflammatory regulation， etc. Kyoto encyclopedia of genes and genomes pathway analysis further indicated that these proteins were mainly concentrated in T cell receptors， B cell receptors， Toll-like receptors， nuclear transcription factor-κB （NF-κB）， Ras proteins， interleukin-17， tumor necrosis factor， phosphatidylinositol 3-kinase/protein kinase B （PI3K-Akt）， mitogen-activated protein kinase （MAPK） and other signaling pathways. Conclusion:The differentially expressed proteins closely related to anti-breast cancer effect of tryptanthrin on 4T1 breast cancer mice are effectively screened out， including up-regulating proteins of leukocyte differentiation antigen 14 （CD14）， prostaglandin G/H synthase 2 （PTGS2）， E3 ubiquitin-protein ligase and down-regulating proteins of CD44， heat shock 70 kDa protein 1A （HSPA1A）， macrophage migration inhibitory factor （MIF）， NF-κB， ribosomal protein S6 kinase alpha-4 （RPS6KA4） and high mobility group protein B1 （HMGB1）. These findings suggest that tryptanthrin can inhibit breast cancer in mice mainly through regulating tumor inflammatory microenvironment.
