The effect of valproic acid in combination with irradiation and temozolomide on primary human glioblastoma cells

摘要: Glioblastoma multiforme (GBM) has nearly uniformly fatal with a median survival of less than 2 years. While there have not been any novel anti-GBM therapeutics approved for many years, the gradual accumulation clinical data suggesting that widely used anti-convulsant agent, valproic acid (VPA) may significantly prolong in GBM patients. This pre-clinical study aimed to determine potential utility VPA treatment GBM. Primary cells were treated as monotherapy and combination temozolomide irradiation. At clinically achievable concentrations, was shown be effective agent five primary lines tested. then sensitizing vitro radiation showed significant augmentation irradiation therapy. In addition, when VPA, combined an additive, rather synergistic effect noted. Gene expression profiling demonstrated close clustering triple mono-treated while untreated clustered closer TMZ-irradiation dual cells. These microarray suggest dominant role at gene level combining these different options. Moreover, vivo tumor transplantation model, we able demonstrate increase animal pre-treated irradiation-VPA treated. findings provide rationale investigation