Integrated proteomics and metabolomics reveals the comprehensive characterization of antitumor mechanism underlying Shikonin on colon cancer patient-derived xenograft model

doi:10.1038/s41598-020-71116-5

	Integrated proteomics and metabolomics reveals the comprehensive characterization of antitumor mechanism underlying Shikonin on colon cancer patient-derived xenograft model
	Chen, Yang 1; Ni, Juan 2,3,4; Gao, Yun 2,3,4; Zhang, Jinghui 1; Liu, Xuesong 1; Chen, Yong 1; Chen, Zhongjian 2,3,4; Wu, Yongjiang 1
刊名	SCIENTIFIC REPORTS
	2020-08-24
卷号	10
ISSN号	2045-2322
DOI	10.1038/s41598-020-71116-5
通讯作者	Chen, Zhongjian(chenzj@zjcc.org.cn) ; Wu, Yongjiang(yjwu@zju.edu.cn)
英文摘要	Colorectal cancer (CRC) is a common malignancy occurring in the digestive system. Despite progress in surgery and therapy options, CRC is still a considerable cause of cancer mortality worldwide. In this study, a colon cancer patient-derived xenograft model was established to evaluate the antitumor activity of Shikonin. The protective effect underlying Shikonin was determined through assessing serum levels of liver enzymes (ALT, AST) and kidney functions (BuN, Scr) in PDX mice. Proteomics and metabolomics profiles were integrated to provide a systematic perspective in dynamic changes of proteins and global endogenous metabolites as well as their perturbed pathways. A total of 456 differently expressed proteins (DEPs), 32 differently expressed metabolites (DEMs) in tumor tissue, and 20 DEMs in mice serum were identified. The perturbation of arginine biosynthesis, purine metabolism, and biosynthesis of amino acids may mainly account for therapeutic mechanism of Shikonin. Furthermore, the expression of mRNAs participating in arginine biosynthesis (CPS1, OTC, Arg1) and do novo purine synthesis (GART, PAICS, ATIC) were validated through RT-qPCR. Our study provides new insights into the drug therapeutic strategies and a better understanding of antitumor mechanisms that might be valuable for further studies on Shikonin in the clinical treatment of colorectal cancer.
资助项目	National Great New Drug Research and Development project[2018ZX09201010] ; National Natural Science Foundation of China[81672315]
WOS关键词	MASS-SPECTROMETRY ; METABOLISM ; THERAPY ; PATHWAY ; CYCLE ; KEGG
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	NATURE RESEARCH
WOS记录号	WOS:000568833100008
资助机构	National Great New Drug Research and Development project ; National Natural Science Foundation of China
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/104094]
专题	中国科学院合肥物质科学研究院
通讯作者	Chen, Zhongjian; Wu, Yongjiang
作者单位	1.Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Peoples R China 2.Chinese Acad Sci, Inst Canc & Basic Med ICBM, Hangzhou 310022, Zhejiang, Peoples R China 3.Univ Chinese Acad Sci, Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China 4.Zhejiang Canc Hosp, Hangzhou 310022, Zhejiang, Peoples R China
推荐引用方式 GB/T 7714	Chen, Yang,Ni, Juan,Gao, Yun,et al. Integrated proteomics and metabolomics reveals the comprehensive characterization of antitumor mechanism underlying Shikonin on colon cancer patient-derived xenograft model[J]. SCIENTIFIC REPORTS,2020,10.
APA	Chen, Yang.,Ni, Juan.,Gao, Yun.,Zhang, Jinghui.,Liu, Xuesong.,...&Wu, Yongjiang.(2020).Integrated proteomics and metabolomics reveals the comprehensive characterization of antitumor mechanism underlying Shikonin on colon cancer patient-derived xenograft model.SCIENTIFIC REPORTS,10.
MLA	Chen, Yang,et al."Integrated proteomics and metabolomics reveals the comprehensive characterization of antitumor mechanism underlying Shikonin on colon cancer patient-derived xenograft model".SCIENTIFIC REPORTS 10(2020).