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挽救SLAMF3表达通过诱导间充质-上皮转化恢复肝癌细胞对索拉非尼的反应。

Rescuing SLAMF3 Expression Restores Sorafenib Response in Hepatocellular Carcinoma Cells through the Induction of Mesenchymal-to-Epithelial Transition.

作者信息

Fouquet Grégory, Marié Constance, Collet Louison, Vilpoux Catherine, Ouled-Haddou Hakim, Nguyen-Khac Eric, Bayry Jagadeesh, Naassila Mickaël, Marcq Ingrid, Bouhlal Hicham

机构信息

Groupe de Recherche sur l'Alcool et les Pharmacodépendances INSERM UMR1247, Centre Universitaire de Recherche en Santé CURS, Université de Picardie Jules Verne, CHU Sud, 80000 Amiens, France.

Laboratoire HEMATIM EA4666, Centre Universitaire de Recherche en Santé CURS, Université de Picardie Jules Verne, CHU Sud, 80000 Amiens, France.

出版信息

Cancers (Basel). 2022 Feb 12;14(4):910. doi: 10.3390/cancers14040910.

DOI:10.3390/cancers14040910
PMID:35205659
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8869973/
Abstract

BACKGROUND

Acquired resistance to sorafenib in hepatocellular carcinoma (HCC) patients results in poor prognosis. Epithelial-to-mesenchymal transition (EMT) is the major mechanism implicated in the resistance to sorafenib. We have reported the tumor suppressor role of SLAMF3 (signaling lymphocytic activation molecules family 3) in HCC progression and highlighted its implication in controlling the MRP-1 transporter activity. These data suggest the implication of SLAMF3 in sorafenib resistance mechanisms.

METHODS

We evaluated the resistance to sorafenib in Huh-7 cells treated with progressive doses (Res cells). We investigated the link between acquired resistance to sorafenib and SLAMF3 expression by flow cytometry and Western blot methods. Furthermore, we analyzed the EMT and the stem cell potential of cells resistant to sorafenib.

RESULTS

Sorafenib resistance was confirmed in Res cells by analyzing the cell viability in the presence of sorafenib. The mesenchymal transition, in Res cells, was confirmed by high migratory index and the expression of EMT antigens. Interestingly, we found that loss of SLAMF3 expression corresponded to sorafenib-resistant phenotypes. The overexpression of SLAMF3 reversed EMT, decreased metastatic potential and inhibited mTOR/ERK1/2 in Res cells.

CONCLUSIONS

We propose that rescuing SLAMF3 expression in resistant cells could represent a potential therapeutic strategy to enhance sorafenib efficacy in HCC patients.

摘要

背景

肝细胞癌（HCC）患者对索拉非尼产生获得性耐药会导致预后不良。上皮-间质转化（EMT）是索拉非尼耐药的主要机制。我们已经报道了信号淋巴细胞激活分子家族3（SLAMF3）在HCC进展中的肿瘤抑制作用，并强调了其在控制多药耐药相关蛋白1（MRP-1）转运体活性中的作用。这些数据提示SLAMF3参与了索拉非尼耐药机制。

方法

我们评估了用递增剂量处理的Huh-7细胞（Res细胞）对索拉非尼的耐药性。我们通过流式细胞术和蛋白质免疫印迹法研究了索拉非尼获得性耐药与SLAMF3表达之间的联系。此外，我们分析了索拉非尼耐药细胞的EMT和干细胞潜能。

结果

通过分析索拉非尼存在时的细胞活力，证实Res细胞对索拉非尼耐药。Res细胞中的间质转化通过高迁移指数和EMT抗原的表达得以证实。有趣的是，我们发现SLAMF3表达缺失与索拉非尼耐药表型相对应。SLAMF3的过表达逆转了EMT，降低了转移潜能，并抑制了Res细胞中的mTOR/ERK1/2。

结论

我们提出，恢复耐药细胞中SLAMF3的表达可能是增强HCC患者索拉非尼疗效的一种潜在治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/5e71bc4ad77a/cancers-14-00910-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/672881976198/cancers-14-00910-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/491de7824910/cancers-14-00910-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/3c68eb2f915a/cancers-14-00910-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/f75cea226b4a/cancers-14-00910-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/214a63abbb82/cancers-14-00910-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/77f55a383dbf/cancers-14-00910-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/5e71bc4ad77a/cancers-14-00910-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/672881976198/cancers-14-00910-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/491de7824910/cancers-14-00910-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/3c68eb2f915a/cancers-14-00910-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/f75cea226b4a/cancers-14-00910-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/214a63abbb82/cancers-14-00910-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/77f55a383dbf/cancers-14-00910-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6923/8869973/5e71bc4ad77a/cancers-14-00910-g007.jpg

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本文引用的文献

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2
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J Tissue Eng Regen Med. 2020 Feb;14(2):257-271. doi: 10.1002/term.2989. Epub 2020 Jan 10.
3
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4
Molecular Links between Cancer and Metabolic Diseases: New Perspectives and Therapeutic Strategies for Cancer Prevention and Treatment by Targeting Nutritional Patterns and Metabolic Alterations.癌症与代谢性疾病之间的分子联系：通过靶向营养模式和代谢改变预防和治疗癌症的新视角与治疗策略
Cancers (Basel). 2023 Feb 20;15(4):1350. doi: 10.3390/cancers15041350.
5
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6
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8
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9
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