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脱氧胆酸对食管腺癌侵袭的影响:对基质金属蛋白酶的影响。

Impact of Deoxycholic Acid on Oesophageal Adenocarcinoma Invasion: Effect on Matrix Metalloproteinases.

机构信息

School of Pharmacy and Pharmaceutical Sciences, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 D02, Ireland.

School of Medicine, Trinity Translational Medicine Institute, Trinity College Dublin, Trinity Centre for Health Sciences, St James's Hospital, Dublin 8 D08, Ireland.

出版信息

Int J Mol Sci. 2020 Oct 28;21(21):8042. doi: 10.3390/ijms21218042.

DOI:10.3390/ijms21218042
PMID:33126685
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7672620/
Abstract

Bile acids (BAs) have been implicated in the development of oesophagitis, Barrett's oesophagus and oesophageal adenocarcinoma (OAC). However, whether BAs promote cancer invasiveness has not been elucidated. We evaluated the role of BAs, in particular deoxycholic acid (DCA), in OAC invasion. Migration and invasiveness in untreated and BA-treated oesophageal SKGT-4 cancer cells were evaluated. Activity and expression of different matrix metalloproteinases (MMPs) were determined by zymography, ELISA, PCR and Western blot. Finally, human OAC tissues were stained for MMP-10 by immunohistochemistry. It was found that SKGT-4 cells incubated with low concentrations of DCA had a significant increase in invasion. In addition, MMP-10 mRNA and protein expression were also increased in the presence of DCA. MMP-10 was found to be highly expressed both in-vitro and in-vivo in neoplastic OAC cells relative to non-neoplastic squamous epithelial cells. Our results show that DCA promotes OAC invasion and MMP-10 overexpression. This study will advance our understanding of the pathophysiological mechanisms involved in human OAC and shows promise for the development of new therapeutic strategies.

摘要

胆汁酸(BAs)与食管炎、巴雷特食管和食管腺癌(OAC)的发展有关。然而,BAs 是否促进癌症侵袭性尚未阐明。我们评估了 BAs,特别是脱氧胆酸(DCA)在 OAC 侵袭中的作用。未处理和 BA 处理的食管 SKGT-4 癌细胞的迁移和侵袭性进行了评估。通过酶谱分析、ELISA、PCR 和 Western blot 测定不同基质金属蛋白酶(MMPs)的活性和表达。最后,通过免疫组织化学法检测 MMP-10 在人 OAC 组织中的染色。结果发现,DCA 孵育的 SKGT-4 细胞侵袭明显增加。此外,DCA 存在时 MMP-10 的 mRNA 和蛋白表达也增加。与非肿瘤性鳞状上皮细胞相比,MMP-10 在体外和体内的肿瘤性 OAC 细胞中均高度表达。我们的研究结果表明,DCA 促进 OAC 的侵袭和 MMP-10 的过表达。这项研究将增进我们对涉及人类 OAC 的病理生理机制的理解,并为开发新的治疗策略提供了希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1794/7672620/5719ed3b858f/ijms-21-08042-g006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1794/7672620/957236a9dcc3/ijms-21-08042-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1794/7672620/f1b3e216a499/ijms-21-08042-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1794/7672620/80cceda6c740/ijms-21-08042-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1794/7672620/5719ed3b858f/ijms-21-08042-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1794/7672620/2ccea67938d6/ijms-21-08042-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1794/7672620/716966dc387d/ijms-21-08042-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1794/7672620/957236a9dcc3/ijms-21-08042-g003.jpg
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