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Resveratrol represses YKL-40 expression in human glioma U87 cells

BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant intracranial tumour that develops in both adults and children. Microarray gene analyses have confirmed that the human YKL-40 gene is one of the most over-expressed genes in these tumours but not in normal brain tissue. Clinical studies...

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Detalles Bibliográficos
Autores principales: Zhang, Wei, Murao, Koji, Zhang, Xiang, Matsumoto, Kensuke, Diah, Suwarni, Okada, Masaki, Miyake, Keisuke, Kawai, Nobuyuki, Fei, Zhou, Tamiya, Takashi
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2988030/
https://www.ncbi.nlm.nih.gov/pubmed/21029458
http://dx.doi.org/10.1186/1471-2407-10-593
Descripción
Sumario:BACKGROUND: Glioblastoma multiforme (GBM) is the most malignant intracranial tumour that develops in both adults and children. Microarray gene analyses have confirmed that the human YKL-40 gene is one of the most over-expressed genes in these tumours but not in normal brain tissue. Clinical studies have shown that serum YKL-40 levels are positively correlated with tumour burden in addition to being an independent prognostic factor of a short relapse-free interval as well as short overall survival in patients with various cancers. Our previous study revealed that YKL-40 was closely correlated with the pathological grades of human primary astrocytomas and played a crucial role in glioma cell proliferation. Hence, YKL-40 could be an attractive target in the design of anti-cancer therapies. METHODS: Cell viability and invasion assays were performed to detect the cell proliferation and invasive ability of U87 cells induced by resveratrol (3, 5, 4'-trihydroxystilbene; Res) or YKL-40 small-interfering RNAs (siRNAs). In addition, the luciferase assay, real-time RT-PCR, western blotting, and ELISA were used to measure YKL-40 promoter activity, mRNA, and protein expression, respectively. The expressions of phosphor-ERK1/2 and ERK1/2 were determined by western blotting. RESULTS: Res inhibited U87 cell proliferation and invasion in vitro and repressed YKL-40 in U87 cells by decreasing the activity of its promoter and reducing mRNA transcription and protein expression in vitro. YKL-40 siRNA treatment also impaired the invasiveness of U87 cells. When U87 cells were cultured with 20 μM PD98059 (an ERK1/2 inhibitor) alone, with 20 μM PD98059 and 100 μM Res, or with 100 μM Res alone for 48 h, YKL-40 protein expression decreased most significantly in the Res-treated group. PD98059 partially reversed the decrease of YKL-40 protein expression induced by Res. Furthermore, phosphor-ERK1/2 expression was reduced by Res treatment in a time-dependent manner. CONCLUSIONS: We demonstrated for the first time that Res represses YKL-40 expression in vitro; in addition, the ERK1/2 pathway is involved in this repression. This finding could extend the prospective use of Res in glioma research and enlarge the armamentarium for treating gliomas.