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麒麟菜的蛋白质组分析揭示了其通过凋亡和铁死亡途径在结肠癌中的作用。

Proteome Analysis of Chi Revealed Its Role in Colon Cancer Through the Apoptosis and Ferroptosis Pathway.

作者信息

Chen Yiwei, Zhang Fan, Du Zhengcai, Xie Jinling, Xia Lei, Hou Xiaotao, Hao Erwei, Deng Jiagang

机构信息

School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, Nanning, China.

出版信息

Front Oncol. 2021 Nov 9;11:727130. doi: 10.3389/fonc.2021.727130. eCollection 2021.

Abstract

Colon cancer is the third most common cancer in the world with a high mortality rate. At present, surgery combined with radiotherapy and chemotherapy is the primary treatment, but patient prognosis remains poor. Traditional Chinese medicine (TCM) has become a complementary and alternative source of anti-cancer drugs. Chi (CNC) is a TCM used to treat a variety of cancers. However, the role of CNC in cancer remains elusive, and its effect and mechanism on colon cancer have not been reported. Here, we show that CNC exerts an excellent inhibitory effect on colon cancer proliferation and apoptosis induction and . We performed label free-based quantitative proteomic analysis to evaluate the HCT116 cells treated with CNC. Our data revealed a total of 363 differentially expressed proteins, of which 157 were up-regulated and 206 down-regulated. Gene Ontology enrichment analysis showed that these proteins were involved in tumor occurrence and development through multiple biological processes such as cell proliferation, cell apoptosis, cell cycle, and cell death. Interestingly, we also found significant changes in ferroptosis pathways. The role of essential proteins glutathione peroxidase 4 (GPX4) and heme oxygenase-1 (HMOX1) were verified. CNC decreased the expression of GPX4 and increased the expression of HMOX1 at the mRNA and protein levels and . Collectively, these findings reveal that CNC regulates colon cancer progression the ferroptosis pathway and could be an attractive treatment for colon cancer.

摘要

结肠癌是全球第三大常见癌症,死亡率很高。目前,手术联合放疗和化疗是主要治疗方法,但患者预后仍然很差。中医药已成为抗癌药物的补充和替代来源。莪术(CNC)是一种用于治疗多种癌症的中药。然而,CNC在癌症中的作用仍不清楚,其对结肠癌的作用及机制尚未见报道。在此,我们表明CNC对结肠癌增殖和诱导凋亡具有优异的抑制作用。我们进行了基于无标记的定量蛋白质组学分析,以评估用CNC处理的HCT116细胞。我们的数据共揭示了363种差异表达蛋白,其中157种上调,206种下调。基因本体富集分析表明,这些蛋白质通过细胞增殖、细胞凋亡、细胞周期和细胞死亡等多个生物学过程参与肿瘤的发生和发展。有趣的是,我们还发现铁死亡途径有显著变化。验证了关键蛋白谷胱甘肽过氧化物酶4(GPX4)和血红素加氧酶-1(HMOX1)的作用。CNC在mRNA和蛋白质水平上降低了GPX4的表达并增加了HMOX1的表达。总的来说,这些发现揭示了CNC通过铁死亡途径调节结肠癌进展,可能是一种有吸引力的结肠癌治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/827e/8630681/2be987ee46c2/fonc-11-727130-g001.jpg

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