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纯化蛋白对SGC-7901人胃癌细胞转移、细胞周期、凋亡及JAK-STAT信号通路的影响。

Effects of purified protein on metastasis, cell cycle, apoptosis and the JAK-STAT signaling pathway in SGC-7901 human gastric cells.

作者信息

Chen Luchao, Lu Zhongxia, Yang Yongle, Du Lijun, Zhou Xiaofang, Chen Yitao

机构信息

Microbiology and Immunology Laboratory, College of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China.

Institute of Preventive and Veterinary Medicine and The Key Laboratory of Animal Virology of Ministry of Agriculture, College of Animal Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, P.R. China.

出版信息

Oncol Lett. 2018 Apr;15(4):4161-4170. doi: 10.3892/ol.2018.7830. Epub 2018 Jan 19.

Abstract

Gastric cancer is one of the most common cancers globally with high rates of morbidity and mortality. Purified protein (pPep) is a protein extracted from the sclerotium of . The present study aimed to investigate the effects of pPep on the viability, migration, cell cycle progression and apoptosis of SGC-7901 cells. The expression of numerous proteins, namely matrix metallopeptidase (MMP)2, MMP9, p53, caspase-3, B-cell lymphoma (Bcl)-2, cyclin A2, cyclin B1, cyclin D1, cyclin dependent kinase (CDK)1, CDK2 and CDK4, were investigated using western blot analysis and reverse transcription-quantitative polymerase chain reaction. The results of the present study demonstrated that treating SGC-7901 cells with pPep markedly suppressed their migration, induced their apoptosis and arrested their progression in S phase. pPep also downregulated the expression of migration-associated proteins (MMP2 and MMP9) and cyclin-associated proteins (cyclin A2, cyclin B1, cyclin D1, CDK1, CDK2 and CDK4) in a dose-dependent manner. Cells treated with pPep significantly upregulated caspase-3 and p53 and downregulated Bcl-2. Finally, the impact of pPep on three key nodes of the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway were investigated and it was revealed that expression levels of JAK1, JAK2 and STAT3 were significantly downregulated following treatment. Together, the results of the present study suggested that pPep suppresses metastasis, arrests cell cycle, induces apoptosis and inhibits the JAK-STAT signaling pathway in SGC-7901 cells. Therefore, pPep may serve as a novel therapeutic agent for patients with gastric cancer.

摘要

胃癌是全球最常见的癌症之一,发病率和死亡率都很高。纯化蛋白(pPep)是从[某种菌核]中提取的一种蛋白质。本研究旨在探讨pPep对SGC-7901细胞活力、迁移、细胞周期进程和凋亡的影响。使用蛋白质印迹分析和逆转录-定量聚合酶链反应研究了多种蛋白质的表达,即基质金属肽酶(MMP)2、MMP9、p53、半胱天冬酶-3、B细胞淋巴瘤(Bcl)-2、细胞周期蛋白A2、细胞周期蛋白B1、细胞周期蛋白D1、细胞周期蛋白依赖性激酶(CDK)1、CDK2和CDK4。本研究结果表明,用pPep处理SGC-7901细胞可显著抑制其迁移,诱导其凋亡并使其在S期的进程停滞。pPep还以剂量依赖性方式下调迁移相关蛋白(MMP2和MMP9)和细胞周期蛋白相关蛋白(细胞周期蛋白A2、细胞周期蛋白B1、细胞周期蛋白D1、CDK1、CDK2和CDK4)的表达。用pPep处理的细胞显著上调半胱天冬酶-3和p53并下调Bcl-2。最后,研究了pPep对Janus激酶(JAK)-信号转导子和转录激活子(STAT)通路三个关键节点的影响,结果显示处理后JAK1、JAK2和STAT3的表达水平显著下调。总之,本研究结果表明pPep可抑制SGC-7901细胞的转移、使细胞周期停滞、诱导凋亡并抑制JAK-STAT信号通路。因此,pPep可能成为胃癌患者的一种新型治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b17/5835924/94dbe36b4151/ol-15-04-4161-g00.jpg

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