Combination of tamoxifen and antisense human telomerase RNA inhibits glioma cell proliferation and anti-apoptosis via suppression of telomerase activity.

Accumulating evidence indicates that telomerase activity and human telomerase RNA (hTR) play a potentially crucial role in maintaining the malignant progression of human gliomas. Tamoxifen (TAM) induces cell growth inhibition by modulating several cellular activities, including signaling pathways and the cell cycle. In this study, we aimed to evaluate the effect of combination therapy with TAM and antisense hTR on malignant glioma growth in vitro. TAM treatment and the down-regulation of hTR expression by antisense hTR resulted in a significant suppression of cell growth and the induction of cell apoptosis through the inhibition of telomerase activity. The antitumor effect of treatment with TAM alone was found to be mediated in part by the down-regulation of telomerase activity and of PKC and IGF-1 expression. Our results indicate that TAM and antisense hTR may serve as a novel strategy for glioma therapy.