title: Gene expression profiling of the anti-glioma effect of Cilengitide.
abstract: Cilengitide (EMD121974), an inhibitor of the adhesive function of integrins, demonstrated preclinical efficacy against malignant glioma. It is speculated that cilengitide can inhibit tumor growth, invasion, and angiogenesis. However, the effects of cilengitide on these processes have not been sufficiently examined. In this study, we investigated the anti-glioma effect of cilengitide using DNA microarray analysis. U87ΔEGFR cells (human malignant glioma cell line) were used for this experiment. The cells were harvested after 16 h of cilengitide treatment, and mRNA was extracted. Gene expression and pathway analyses were performed using a DNA microarray (CodeLink™Human Whole Genome Bioarray). The expression of 265 genes was changed with cilengitide treatment. The expression of 214 genes was up-regulated by more than 4-fold and the expression of 51 genes was down-regulated by more than 4-fold compared to the controls. In pathway analysis, "apoptotic cleavage of cellular proteins" and "TNF receptor signaling pathway" were over-represented. Apoptotic-associated genes such as caspase 8 were up-regulated. Gene expression profiling revealed more detailed mechanism of the anti-glioma effect of cilengitide. Genes associated with apoptosis were over-represented following cilengitide treatment.
authors.affiliation: Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558 Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Onishi
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kurozumi
authors.forename: Tomotsugu
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Michiue
authors.forename: Kentaro
authors.initials: K
authors.lastname: Fujii
authors.forename: Joji
authors.initials: J
authors.lastname: Ishida
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Shimazu
authors.forename: E Antonio
authors.initials: EA
authors.lastname: Chiocca
authors.forename: Balveen
authors.initials: B
authors.lastname: Kaur
authors.forename: Isao
authors.initials: I
authors.lastname: Date
keywords: Apoptosis; Cilengitide; Gene expression profiling; Glioma; Integrin