Human corticotrophin releasing factor inhibits cell proliferation and promotes apoptosis through upregulation of tumor protein p53 in human glioma

摘要

Corticotropin-releasing factor (CRF) and its receptors have been detected in numerous tumors and have an important role in tumorigenesis and proliferation. However, the role of these peptides has not been established in human glioma and malignant glioma cell lines. The present study evaluated for the first time, the expression of CRF receptor 1 (CRFR1) in 35 human glioma samples, 13 normal brain tissues and human U87 glioma cells using immunohistochemistry, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. Levels of CRFR1 were identified to be significantly increased in human glioma and U87 cells and higher levels of CRFR1 were observed in glioma tissues of higher grade. The biological functions of human CRF (hCRF) on U87 cells glioma cells were investigated by cell counting, a bromodeoxyuridine assay and flow cytometry. The U87 cells under hCRF treatment exhibited reduced proliferation, increased apoptosis and a cell cycle arrest in S and G2/M phase. The tumor protein p53 (p53) gene may participate in the activation of hCRF via CRFR1 in U87 cells, therefore p53 mRNA and protein were evaluated using RT-qPCR and western blot analysis. Finally, the present results suggest that hCRF inhibits proliferation and induces cell-cycle arrest and apoptosis in U87 cells via the CRFR1-mediated p53 signaling pathway. Therefore, the present study also suggests that hCRF may be used therapeutically, and CRFR1 may be a putative therapeutic target for human glioma.