HOXB9 inhibits proliferation in gastric carcinoma cells via suppression of phosphorylated-Akt and NF-κB-dependent Snail expression

HOXB9 inhibits proliferation in gastric carcinoma cells via suppression of phosphorylated-Akt and NF-κB-dependent Snail expression
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HOXB9 通过抑制磷酸化 Akt 和 NF-κ B 依赖性 Snail 表达来抑制胃癌细胞增殖

DOI:
10.1016/j.dld.2018.08.018
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发表时间:
2019-01-01
影响因子:
4.5
通讯作者:
Chang, Qing
Chang, Qing
中科院分区:
医学2区
文献类型:
--
作者:
Zhang, Li;Wu, Qinghua;Chang, Qing

文献摘要

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背景:HOXB 9是一种同源异型盒转录因子,在肿瘤的发生发展中起重要作用。这种蛋白质已被证明可以抑制癌细胞增殖。然而,HOXB 9介导的抑制细胞增殖的机制仍有待阐明。方法:在这项研究中,两个胃癌细胞株,SGC 7901和MKN 45,转染质粒pLVX-HOXB 9和shHOXB 9。结果:与MKN 45/shHOXB 9细胞相比,HOXB 9基因在SGC 7901/HOXB 9细胞中的过表达可导致SGC 7901/HOXB 9细胞的凋亡率增加,并降低其转移能力。此外,在SGC 7901/HOXB 9细胞中观察到磷酸化Akt蛋白的表达减少,而在MKN 45/shHOXB 9细胞中观察到相同蛋白的表达增加。我们还观察到HOXB 9介导NF-κ B和N-钙粘蛋白以及Snail蛋白表达的减少。相反,HOXB 9引起E-cadherin.Conclusions的表达增加:总之,本研究报告HOXB 9可以抑制磷酸化Akt的表达和NF-κ B B活性。后者影响Snail蛋白的表达和胃癌增殖的抑制。(C)2018由Elsevier Ltd代表Editrice Gastroenterologica Italiana S.r.l.
Background: HOXB9 is a homeobox transcription factor which plays an important role in carcinoma development. This protein has been shown to inhibit cancer cell proliferation. However, the mechanisms that underpin HOXB9-mediated inhibition of cellular proliferation remain to be elucidated.Methods: In this study, two gastric cancer cell lines, SGC7901 and MKN45, were transfected with plasmids pLVX-HOXB9 and shHOXB9. These transfections resulted in the over-expression of the HOXB9 gene in the SGC7901/HOXB9 cells and knockdown of the HOXB9 gene in the MKN45/shHOXB9 cells.Results: Over-expression of the HOXB9 gene in the SGC7901/HOXB9 cells caused an increase in the apoptotic rate and a concomitant reduction in metastatic ability compared with the knocked-down MKN45/shHOXB9 cells. Moreover, a reduction in the expression of the phosphorylated-Akt protein was observed in the SGC7901/HOXB9 cells, while an increase in expression of the same protein was observed in the MKN45/shHOXB9 cells. We also observed that HOXB9 mediated a reduction in both NF-kappa B and N-cadherin and Snail protein expression. Conversely, HOXB9 caused an increase in the expression of E-cadherin.Conclusions: In summary, this study reports that HOXB9 can suppress both phosphorylated-Akt expression and NF-kappa B activity. The latter phenomenon affects Snail protein expression and the inhibition of gastric carcinoma proliferation. (C) 2018 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l.