GSE110130
Suppression of glioblastoma by a drug cocktail inducing tumor cells toward a neuronal fate
Glioblastoma (GBM), the most common and aggressive malignant tumor in adult brain, is a notoriously fatal tumor. For many years, surgical resection and postoperative radiotherapy had been used for the treatment of GBM, which resulted in a poor median survival of about 12 months. Currently, Temozolomide (TMZ) as a clinically meaningful chemotherapy drug has become the standard first-line treatment for GBM, but with an increase of the median survival for about only 2.5 months. In this study, encouraged by previous findings that human astrocytes could be converted into neuronal cells with small molecules and that human GBM cells could be induced into neuronal like cells by transcription factors, we intended to test whether GBM cells could be induced into neuronal like cells by a cocktail of approved drugs and whether this drug cocktail help to suppress GBM in patient derived xenograft (PDX). Here we screened and identified TMZ, Tranilast, and Fasudil, three approved clinical drugs (TTF), to induce GBM cells toward a neuronal fate. Both serum and serum-free cultured GBM cells exhibited neuronal morphology and expressed neuronal genes under TTF treatment. Malignant properties including uncontrolled proliferation and intensive invasion of GBM cells were also attenuated with TTF treatment. Most importantly, when administrated in PDX, TTF cocktail significantly suppressed GBM growth in vivo and prolonged the survival of tumor-bearing mice, as compared to TMZ alone. Our study indicated that using the approved drug cocktail to induce tumor cells toward a neuronal fate might be a clinically promising strategy for GBM treatment. Overall design: In this data set, we include RNA-Seq data of human glioblastoma cells treated with a drug cocktail (TMZ, Tranilast, and Fasudil) for 0, 2, and 10 days, as well as human neurons