Over-expression of ARHI decreases tumor growth, migration, and invasion in human glioma

Abstract

This study was conducted to evaluate the role of tumor suppressor gene ras homologue member I (ARHI) in human glioma tumors. We examined expression of ARHI in human glioma tumors and normal brain tissue and also in 4 different glioma cell lines. Furthermore, the effects of ARHI over-expression produced by cellular transfection on the growth of human glioma U251 cells cultured in vitro were also studied. Expression of ARHI was evaluated in samples of glioma tumors obtained from 59 patients who underwent surgery at the Department of Neurosurgery, Fujian Medical University Union Hospital, Fuzhou, China. Ten samples of normal brain tissue were used as controls. Additionally, in vitro studies were conducted in which a recombinant vector carrying ARHI cDNA was constructed and transfected into U251 glioma cells with reduced expression of ARHI. Following transfection, the MTT assay, flow cytometry, TUNEL procedure, Transwell assay, and wound-healing test were employed to evaluate the biological functions of ARHI in U251 glioma cells in vitro. Analyses of mRNA and protein expression revealed that ARHI was significantly down-regulated in glioma tissues as well as in 4 malignant glioma cell lines. Over-expression of ARHI resulted in suppression of glioma cell proliferation, arrest of cell cycle progression, reduction in cell migration and invasion, and promotion of cell apoptosis. Collectively, our data highlight the importance of ARHI in glioma progression and provide the first biological basis for ARHI as a novel candidate target for gene therapy of glioma.