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7-甲氧基-1-四氢萘酮通过调节c-Met、p-AKT、NF-κB、MMP2和MMP9的表达诱导肝癌细胞凋亡、抑制细胞增殖和迁移。

7-Methoxy-1-Tetralone Induces Apoptosis, Suppresses Cell Proliferation and Migration in Hepatocellular Carcinoma via Regulating c-Met, p-AKT, NF-κB, MMP2, and MMP9 Expression.

作者信息

Wen Ying, Cai Xiaoyan, Chen Shaolian, Fu Wei, Chai Dong, Zhang Huainian, Zhang Yongli

机构信息

Guangzhou Key Laboratory of Construction and Application of New Drug Screening Model Systems, Guangdong Pharmaceutical University, Guangzhou, China.

Department of Cell Biology and Medical Genetics, School of Life Sciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou, China.

出版信息

Front Oncol. 2020 Feb 7;10:58. doi: 10.3389/fonc.2020.00058. eCollection 2020.

Abstract

This study aimed to determine the anti-proliferative and anti-migratory effects of 7-methoxy-1-tetralone (MT) in hepatocellular carcinoma (HCC) cells. MTT assay assessed HCC cell viability; cell apoptosis of HCC cells was determined by flow cytometry; wound healing assay evaluated HCC cell migratory ability; protein expression levels were assessed using western blot assay; the antitumor effects of MT were tested in BALB/c nude mice and the pathological changes within the tumor tissues were evaluated by immunohistochemistry. MT treatment significantly suppressed the cell proliferative and migratory potentials of HepG2 cells, and induced HepG2 cell apoptosis. The western blot assay showed that MT treatment caused a suppression on c-Met, phosphorylated AKT (p-AKT), NF-κB, matrix metallopeptidase 2 (MMP2)/MMP9 protein levels in HepG2 cells. Further animal studies deciphered that MT treatment suppressed tumor growth of HepG2 cells in the nude mice, but had no effect on the body weight and the organ index of liver and spleen. Further immunohistochemistry analysis of the dissected tumor tissues showed that MT treatment significantly suppressed the protein expression levels of NF-κB, MMP9, MMP2, and p-AKT. In summary, the present study demonstrated the anti-tumor effects of MT on the HCC, and MT suppressed HCC progression possibly via regulating proliferation- and migration-related mediators including c-Met, p-AKT, NF-κB, MMP2, and MMP9 in HepG2 cells.

摘要

本研究旨在确定7-甲氧基-1-四氢萘酮(MT)对肝癌(HCC)细胞的抗增殖和抗迁移作用。MTT法评估HCC细胞活力;通过流式细胞术测定HCC细胞凋亡;伤口愈合试验评估HCC细胞迁移能力;使用蛋白质印迹法评估蛋白质表达水平;在BALB/c裸鼠中测试MT的抗肿瘤作用,并通过免疫组织化学评估肿瘤组织内的病理变化。MT处理显著抑制了HepG2细胞的增殖和迁移能力,并诱导了HepG2细胞凋亡。蛋白质印迹分析表明,MT处理导致HepG2细胞中c-Met、磷酸化AKT(p-AKT)、NF-κB、基质金属蛋白酶2(MMP2)/MMP9蛋白水平受到抑制。进一步的动物研究表明,MT处理抑制了裸鼠中HepG2细胞的肿瘤生长,但对体重以及肝脏和脾脏的器官指数没有影响。对解剖的肿瘤组织进行的进一步免疫组织化学分析表明,MT处理显著抑制了NF-κB、MMP9、MMP2和p-AKT的蛋白质表达水平。总之,本研究证明了MT对HCC的抗肿瘤作用,并且MT可能通过调节HepG2细胞中与增殖和迁移相关的介质(包括c-Met、p-AKT、NF-κB、MMP2和MMP9)来抑制HCC进展。

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