Beta-Elemene Inhibits Proliferation Of Human Glioblastoma Cells Through The Activation Of Glia Maturation Factor Beta And Induces Sensitization To Cisplatin

beta-elemene, a natural drug extracted from Curcuma wenyujin, strongly inhibits glioblastoma growth. However, the mechanism of beta-elemene antitumor action remains unclear. Glia maturation factor beta (GMF beta) regulates cellular growth, fission, differentiation and apoptosis. It has been reported that overexpression of GMF beta inhibits the growth of glioblastoma cells and decreases tumor volume. To illustrate the role of GMF beta in the anti-proliferative effect of beta-elemene in glioblastoma, U87 cells were treated with beta-elemene at various doses and for different periods of time, and levels of phospho-GMF beta (p-GMF beta) and total GMF beta were determined by immunoprecipitation and Western blot analysis. Upon GMF beta silencing using RNA interference, the antitumor action of beta-elemene was evaluated in a methyl thiazolyl tetrazolium assay and by semi-quantitative Western blot analysis of MKK3/6 and p-MKK3/6 expression. Finally, chemosensitization to cisplatin by beta-elemene was examined using a cell counting array, and the cell growth inhibitory rate was calculated. The results showed that beta-elemene inhibits U87 cell viability through the activation of the GMF beta signaling pathway. Conversely, silencing the expression of GMF beta reversed the antitumor effect of beta-elemene and impaired the phosphorylation of MKK3/6. Furthermore, beta-elemene increased the sensitivity of U87 glioblastoma cells to the chemotherapeutic agent cisplatin. Taken together, these results suggest that activation of the GMF beta pathway mediates the antitumor effect of beta-elemene in glioblastoma. GMF beta is a putative molecular target for glioblastoma therapy.