goserelin and Glioblastoma

Gonadotropin-releasing hormone (GnRH) receptor, a rhodopsin-like G-protein coupled receptor (GPCR) family member involved in GnRH signaling, is reported to be expressed in several tumors including glioblastoma multiforme (GBM), one of the most malignant and aggressive forms of primary brain tumors. However, the molecular targets associated with GnRH receptor are not well studied in GBM or in other cancers. The present study aims at investigating the effect of GnRH agonist (Gosarelin acetate) on cell proliferation and associated signaling pathways in GBM cell line, LN229.. The treatment with different concentrations of GnRH agonist showed a reduction in cell proliferation with a maximum reduction of 48.2% observed at 10. The study suggests a possible link of GnRH signaling with EGFR signaling pathways likely via KNG1. KNG1 inhibitors may be investigated independently or in combination with GnRH agonist for therapeutic applications.

Topics: Animals; Antineoplastic Agents, Hormonal; Brain Neoplasms; Cell Line, Tumor; Cell Proliferation; Chromatography, Liquid; Computational Biology; Glioblastoma; Gonadotropin-Releasing Hormone; Goserelin; Humans; Proteomics; Receptors, LHRH; Signal Transduction; Tandem Mass Spectrometry

Malignant glioblastoma is one of the highest proliferative and invasive tumors within the central nervous system (CNS); the therapeutical options for this disease are still very poor. Receptors for gonadotropin-releasing hormone (GnRH) have been reported to be present in glioblastoma tissues. This study aimed to determine the role of these receptors in the control of glioma growth. In two human glioblastoma cell lines, U87MG and U373, we demonstrated the expression of GnRH receptors, both at mRNA and protein levels. We also found that GnRH receptor is expressed in glioblastoma tissues from tumor patients as shown by Western blotting. In U87MG and U373 cell lines, we found the expression of mRNA for GnRH, indicating the presence of an autocrine GnRH-based system in these cell lines. Treatment of the two cell lines with a GnRH agonist resulted in a significant decrease of cell proliferation. Moreover, the GnRH agonist significantly counteracted the forskolin-induced increase of intracellular cAMP levels in these cells. These findings suggest that the GnRH receptor might represent a molecular target for an endocrine therapeutical approach against gliomas.

Topics: Antineoplastic Agents, Hormonal; Cell Growth Processes; Cell Line, Tumor; Cyclic AMP; Glioblastoma; Gonadotropin-Releasing Hormone; Goserelin; Humans; Receptors, LHRH; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger