ABSTRACT
Glioma is one of the most common malignancies in the world. However, an effective regiment is lacking. Increasing evidence indicated that PI3K/AKT signaling is critical for the survival of glioma. In this study, we aimed to study the effect of aplysin on the survival and proliferation of GL26 glioma cells and the involved mechanisms. The data showed that aplysin suppressed the viability of glioma cells in both dose- and time-dependent manners. It also induced G0/G1 arrest and apoptosis in glioma cells. Western blot assays revealed that aplysin treatment changed p-AKT expression by impairing the formation of Heat shock protein 90/AKT complex. Aplysin significantly increased the survival time of mice-bearing glioma and reduced the weights of the established gliomas. Collectively, aplysin can inhibit the proliferation of GL26 glioma cells and induce apoptosis in vitro, perhaps through suppressing PI3K/AKT pathway. It can also inhibit glioma growth in vivo and prolong the survival of mice. Thus, aplysin may be a novel therapeutic drug for glioma.
Subject(s)
Apoptosis/drug effects , Brain Neoplasms/pathology , Glioma/pathology , HSP90 Heat-Shock Proteins/metabolism , Hydrocarbons, Brominated/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Sesquiterpenes/pharmacology , Animals , Brain Neoplasms/enzymology , Brain Neoplasms/metabolism , Cell Line, Tumor , Glioma/enzymology , Glioma/metabolism , Humans , Mice , Mice, Inbred C57BLABSTRACT
PURPOSE: Aplysin, a natural brominate compound from marine organisms, has been demonstrated to exhibit anti-tumor activity, mainly by inducing apoptosis and cell cycle arrest. However, its effect on glioma is still unknown. In this study, we evaluated the effects of aplysin on the malignant properties of glioma cells and its enhancing effect on temozolomide (TMZ) action against drug-resistant glioma cell lines. METHODS: We employed several human glioma cell lines and primary glioma cells to address this issue with multidisciplinary approaches. RESULTS: The combined application of aplysin and TMZ significantly sensitizes glioma cells to TMZ action, compared with TMZ alone. miRNA profile analysis revealed that the abundance of miR-181, an important glioma tumor suppressors believed to enhance TMZ effect, was greatly elevated in aplysin-treated glioma cell lines. The aplysin-induced TMZ sensitivity is dependent on MEK1 in glioma cells. Overexpression of MEK1 was able to abolish the effect of aplysin on glioma cells. CONCLUSIONS: We found that aplysin can enhance the effect of TMZ on glioma cells by increasing miR-181 expression.
