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-介导单纯疱疹病毒胸苷激酶/更昔洛韦治疗抑制小鼠模型中的癌症转移。

-Mediated Herpes Simplex Virus-TK/Ganciclovir Treatment Inhibits Cancer Metastasis in Mouse Model.

机构信息

Department of Biochemistry & Molecular Biology, Molecular Medicine & Cancer Research Center, College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.

出版信息

Int J Mol Sci. 2023 Jul 21;24(14):11721. doi: 10.3390/ijms241411721.

Abstract

Previous studies have found that -mediated herpes simplex virus-TK/ganciclovir (BF-TK/GCV) reduces the expression of VEGF and CD146, implying tumor metastasis inhibition. However, the mechanism by which BF-TK/GCV inhibits tumor metastasis is not fully studied. Here, we comprehensively identified and quantified protein expression profiling for the first time in gastric cancer (GC) cells MKN-45 upon BF-TK/GCV treatment using quantitative proteomics. A total of 159 and 72 differential expression proteins (DEPs) were significantly changed in the BF-TK/GCV/BF-TK and BF-TK/GCV/BF/GCV comparative analysis. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis enriched some metastasis-related pathways such as gap junction and cell adhesion molecules pathways. Moreover, the transwell assay proved that BF-TK/GCV inhibited the invasion and migration of tumor cells. Furthermore, immunohistochemistry (IHC) demonstrated that BF-TK/GCV reduced the expression of HIF-1α, mTOR, NF-κB1-p105, VCAM1, MMP13, CXCL12, ATG16, and CEBPB, which were associated with tumor metastasis. In summary, BF-TK/GCV inhibited tumor metastasis, which deepened and expanded the understanding of the antitumor mechanism of BF-TK/GCV.

摘要

先前的研究发现,-介导的单纯疱疹病毒胸苷激酶/更昔洛韦(BF-TK/GCV)降低了 VEGF 和 CD146 的表达,暗示肿瘤转移抑制。然而,BF-TK/GCV 抑制肿瘤转移的机制尚未完全研究。在这里,我们首次使用定量蛋白质组学技术,全面鉴定并定量了 BF-TK/GCV 处理胃癌(GC)细胞 MKN-45 后的蛋白质表达谱。在 BF-TK/GCV/BF-TK 和 BF-TK/GCV/BF/GCV 比较分析中,共有 159 个和 72 个差异表达蛋白(DEPs)显著改变。京都基因与基因组百科全书(KEGG)通路分析富集了一些与转移相关的途径,如间隙连接和细胞黏附分子途径。此外,Transwell 测定证明 BF-TK/GCV 抑制了肿瘤细胞的侵袭和迁移。此外,免疫组织化学(IHC)显示 BF-TK/GCV 降低了与肿瘤转移相关的 HIF-1α、mTOR、NF-κB1-p105、VCAM1、MMP13、CXCL12、ATG16 和 CEBPB 的表达。综上所述,BF-TK/GCV 抑制肿瘤转移,加深并扩展了对 BF-TK/GCV 抗肿瘤机制的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/765c/10380465/305a902361f4/ijms-24-11721-g001.jpg

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