The effects of tibolone on the human primary glioblastoma multiforme cell culture and the rat C6 glioma model

Abstract

Objectives: In the light of recent advances in tumor biology and genetics, we hypothesized that tibolone, an estrogen receptor agonist, may have antiproliferative effects on primary human glioblastoma cells and rat C6 malignant glioma cell lines. We thought that tibolone should exert its antiproliferative effects by augmenting glial cell differentiation through the naive, nonhypermethylated estrogen receptors in the glioma cells.Methods: Human primary glioblastoma multiforme (GBM) cells were acquired perioperatively from ten patients aged between 45 and 69 years, diagnosed clinically and radiologically with GBM. The diagnosis was confirmed using immunohistochemical assays. Human GBM and rat C6 malignant glioma cells were cultivated in vitro to obtain monolayer cell cultures. Tibolone was then applied to these cultures in wells, each containing 500,000 tumor cells.Results: Tibolone significantly decreased the number of human GBM cells at the concentrations of 10 and 100 mg/ml. For tibolone, a strong dose-dependent correlation in tumor inhibition was found (p=0.001). This antiproliferative effect of tibolone in human GBM cells was not observed in rat C6 malignant glioma cells. Tibolone demonstrated differential effects on human GBM and rat C6 glioma cells.Discussion: In vitro antiproliferative effects of tibolone on human GBM need to be investigated further in in vivo works.