Effects of silibinin on cell growth and invasive properties of a human hepatocellular carcinoma cell line, HepG-2, through inhibition of extracellular signal-regulated kinase 1/2 phosphorylation
Effects of silibinin on cell growth and invasive properties of a human hepatocellular carcinoma cell line, HepG-2, through inhibition of extracellular signal-regulated kinase 1/2 phosphorylation
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DOI：
10.1016/j.ejphar.2008.06.011
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发表时间：
2008-09-04
影响因子：
5
通讯作者：
Nooridaloii, Mohammad R.
中科院分区：
文献类型：
--
作者：
Momeny, Majid;Khorramizadeh, Mohammad R.;Nooridaloii, Mohammad R.
本研究的目的是评估水飞蓟宾对人肝癌HepG-2细胞的影响。采用微量四氮唑试验（MTT法）、乳酸脱氢酶（LDH）释放、明胶酶谱、格里斯反应、细胞外信号调节激酶（ERK）1/2磷酸化试验和实时定量RT-PCR评价水飞蓟宾对细胞增殖、细胞毒性、转移潜能、一氧化氮（NO）产生、ERK 1/2磷酸化和激活的影响。在 HepG-2 细胞中。水飞蓟宾抑制细胞增殖、基质金属蛋白酶2酶活性。 NO 产生和 ERK 1/2 磷酸化呈剂量依赖性，且不产生任何细胞毒性作用。此外，还观察到 Raf 激酶抑制剂蛋白 (RKIP)、具有 EVH-1 结构域的芽苗相关蛋白 1 (Spred-1)、具有 EVH-1 结构域的芽苗相关蛋白 2 (Spred-2) 的 mRNA 水平表达增加，同时癌症中高表达的 (Hec1) 和 MMP-2 的转录水平显着降低。总之，这些问题首次表明水飞蓟宾治疗可以通过直接（通过抑制ERK 1/2磷酸化）和间接（通过上调RKIP、Spred-1和Spred-2）抑制ERK 1/2级联来抑制HepG-2细胞的细胞增殖和侵袭潜力。此外，水飞蓟宾可能通过下调 Hec1 来抑制细胞生长和增殖。 (C) 2008 Elsevier B.V. 保留所有权利。
The purpose of the current study is to evaluate the effect of silibinin on human hepatocellular carcinoma HepG-2 cells. Microculture tetrazolium test (MTT assay), Lactate dehydrogenase (LDH) release, Gelatin zymography, Griess reaction, Cell-based the extracelluar signal-regulated kinase (ERK) 1/2 phosphorylation assay and quantitative real-time RT-PCR were employed to appraise the effect of silibinin on cell proliferation, cytotoxicity, metastatic potential, nitric oxide (NO) production, ERK 1/2 phosphorylation and activation in HepG-2 cells. Silibinin inhibited cell proliferation, matrix metalloproteinase 2 enzymatic activity. NO production and ERK 1/2 phosphorylation in a dose-dependent manner without exerting any cytotoxicity effect. In addition, an expressive increase in mRNA levels of Raf kinase inhibitor protein (RKIP), sprouty-related protein 1 with EVH-1 domain (Spred-1), sprouty-related protein with EVH-1 domain 2 (Spred-2) coupled with a significant reduction in transcriptional levels of highly expressed in cancer (Hec1) and MMP-2 were observed. Altogether, these issues show for the first time that silibinin treatment could inhibit cell proliferation and invasive potential of HepG-2 cells through inhibition of ERK 1/2 cascade both directly (through suppression of ERK 1/2 phosphorylation) and indirectly (through up-regulation of RKIP, Spred-1 and Spred-2). In addition, cell growth and proliferation may be inhibited by silibinin through down-regulation of Hec1. (C) 2008 Elsevier B.V. All rights reserved.