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通过抑制丝裂原活化蛋白激酶(MAPK)信号通路的过度激活,抑制胃癌细胞的增殖、迁移、侵袭及肿瘤生长。

Over-expression of suppressed cell proliferation, migration, invasion, and tumor growth in gastric cancer by restraining over-activation of MAPK signaling pathways.

作者信息

Li Yan, Ji Shan, Fu Liye, Jiang Tao, Wu Di, Meng Fandong

机构信息

Department of Biotherapy, Cancer Research Institute, the First Affiliated Hospital of China Medical University, Shenyang City, People's Republic of China.

Department of Endocrinology, The Fifth People's Hospital of Shenyang City, Shenyang City, People's Republic of China.

出版信息

Onco Targets Ther. 2018 Jan 9;11:279-290. doi: 10.2147/OTT.S130255. eCollection 2018.

Abstract

Globally, gastric cancer is the second-greatest cause of cancer death. belongs to the Rho family of GTPases which is involved in cellular migration, invasion, and growth phases. The aim of the present study was to investigate whether could regulate cell proliferation, migration, invasion, and related molecular mechanisms in gastric cancer. Cell Counting Kit-8 (CCK-8) assay results showed that following transfection of a recombinant plasmid, over-expression of inhibited cell viability in MGC-803 and BGC823 cells. Using in vitro transwell analysis, migration and invasion abilities were significantly inhibited in cells with high expression. Phosphorylation levels of ERK, JNK, and p38 by Western blot analysis significantly declined after transfection of cells with the plasmid. Expression levels of ROCK, MTA1, and MMP-2/9 were detected by real-time polymerase chain reaction and Western blotting, and over-expression of decreased the expression levels of ROCK, MTA1, and MMP-9. A further in vivo tumor formation study in nude mice indicated that over-expression of delayed the progress of tumor formation. These results indicate that could act as a tumor suppressor and may serve as a promising therapeutic strategy for gastric cancer.

摘要

在全球范围内,胃癌是癌症死亡的第二大原因。属于Rho GTP酶家族,参与细胞迁移、侵袭和生长阶段。本研究的目的是探讨是否能调节胃癌细胞的增殖、迁移、侵袭及相关分子机制。细胞计数试剂盒-8(CCK-8)检测结果显示,转染重组质粒后,的过表达抑制了MGC-803和BGC823细胞的活力。通过体外Transwell分析,高表达细胞的迁移和侵袭能力显著受到抑制。用质粒转染细胞后,通过蛋白质印迹分析,ERK、JNK和p38的磷酸化水平显著下降。通过实时聚合酶链反应和蛋白质印迹检测ROCK、MTA1和MMP-2/9的表达水平,的过表达降低了ROCK、MTA1和MMP-9的表达水平。在裸鼠中进行的进一步体内肿瘤形成研究表明,的过表达延缓了肿瘤形成的进程。这些结果表明,可作为一种肿瘤抑制因子,可能为胃癌提供一种有前景的治疗策略。 (注:原文中“ belongs to the Rho family of GTPases which is involved in cellular migration, invasion, and growth phases.”以及多处出现的“ ”指代不明,翻译时保留原文形式。)

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3b18/5767098/f94da87e14b0/ott-11-279Fig1.jpg

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