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Over-expression of ARHGAP18 suppressed cell proliferation, migration, invasion, and tumor growth in gastric cancer by restraining over-activation of MAPK signaling pathways

Authors Li Y, Ji S, Fu L, Jiang T, Wu D, Meng F

Received 14 December 2016

Accepted for publication 19 May 2017

Published 9 January 2018 Volume 2018:11 Pages 279—290

DOI https://doi.org/10.2147/OTT.S130255

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Prof. Dr. Geoffrey Pietersz


Yan Li,1 Shan Ji,2 Liye Fu,1 Tao Jiang,1 Di Wu,1 Fandong Meng1

1Department of Biotherapy, Cancer Research Institute, the First Affiliated Hospital of China Medical University, Shenyang City, People’s Republic of China; 2Department of Endocrinology, The Fifth People’s Hospital of Shenyang City, Shenyang City, People’s Republic of China

Abstract: Globally, gastric cancer is the second-greatest cause of cancer death. ARHGAP18 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 ARHGAP18 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 ARHGAP18 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 ARHGAP18 expression. Phosphorylation levels of ERK, JNK, and p38 by Western blot analysis significantly declined after transfection of cells with the ARHGAP18 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 ARHGAP18 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 ARHGAP18 delayed the progress of tumor formation. These results indicate that ARHGAP18 could act as a tumor suppressor and may serve as a promising therapeutic strategy for gastric cancer.

Keywords: ARHGAP18, gastric cancer, cell proliferation, migration, invasion, MAPK

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