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柳氮磺胺吡啶通过抑制 xCT 抑制胃癌增殖和转移:传统药物的新用途。

Sulfasalazine, a potent suppressor of gastric cancer proliferation and metastasis by inhibition of xCT: Conventional drug in new use.

机构信息

Department of Colorectal Surgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China.

出版信息

J Cell Mol Med. 2021 Jun;25(12):5372-5380. doi: 10.1111/jcmm.16548. Epub 2021 May 14.

Abstract

The aim of this study was to explore the role of sulfasalazine on proliferation and metastasis in gastric cancer by inhibition of xCT. The relationships between clinical characteristics and xCT expression were analysed. An immunohistochemical staining assay and Western blot were performed among gastric cancers and normal gastric tissues. qPCR and Western blot were also used to evaluate the mRNA and protein expression in the normal gastric cell and eight gastric cancer cells, respectively. CCK-8 and colony formation assays were used to evaluate the effect of sulfasalazine on the proliferation and colony formation ability of three gastric cancers. The effect of sulfasalazine on the migration and invasion abilities of three cancer cells was assessed by the Transwell assay. xCT protein is up-regulated in gastric cancer specimens and cells. Three gastric cancer cells with high, medium and low expression of xCT were selected for the following analyses. CCK-8 assays revealed that sulfasalazine could attenuate the proliferation of HGC-27 and AGS. Also, the colony formation assay revealed that sulfasalazine might attenuate the colony formation ability in HGC-27 and AGS cells. Plus, the Transwell assays demonstrated that sulfasalazine might attenuate the migration and invasion abilities in HGC-27 and AGS cells. In conclusion, higher expression of xCT is associated with advanced tumour stage and poor overall survival of gastric cancer. Sulfasalazine can attenuate the proliferation, colony formation, metastasis and invasion of gastric cancer in vitro. Further study is required to validate our findings.

摘要

本研究旨在通过抑制 xCT 探讨柳氮磺胺吡啶对胃癌增殖和转移的作用。分析 xCT 表达与临床特征的关系。采用免疫组织化学染色和 Western blot 检测胃癌和正常胃组织中 xCT 的表达。qPCR 和 Western blot 分别用于评估正常胃细胞和 8 种胃癌细胞中的 mRNA 和蛋白表达。CCK-8 和集落形成实验用于评估柳氮磺胺吡啶对三种胃癌细胞增殖和集落形成能力的影响。Transwell 实验评估柳氮磺胺吡啶对三种癌细胞迁移和侵袭能力的影响。xCT 蛋白在胃癌标本和细胞中上调。选择 xCT 高、中、低表达的三种胃癌细胞进行以下分析。CCK-8 实验表明柳氮磺胺吡啶可减弱 HGC-27 和 AGS 的增殖。此外,集落形成实验表明柳氮磺胺吡啶可能减弱 HGC-27 和 AGS 细胞的集落形成能力。此外,Transwell 实验表明柳氮磺胺吡啶可能减弱 HGC-27 和 AGS 细胞的迁移和侵袭能力。总之,xCT 高表达与胃癌晚期肿瘤分期和总生存期不良相关。柳氮磺胺吡啶可减弱胃癌细胞体外增殖、集落形成、转移和侵袭。需要进一步研究来验证我们的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cc9/8184680/089c5f55205b/JCMM-25-5372-g001.jpg

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