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