Abstract
Glioblastoma (GBM) is the most common and malignant intracranial tumor in adults. Despite continuous improvements in diagnosis and therapeutic method, the prognosis is still far away from expectations. The invasive phenotype of GBM is the main reason for the poor prognosis. Epithelial-mesenchymal transition (EMT) is recognized as a participator in this invasive phenotype. Resveratrol, a natural plant-derived compound, is reported to be able to regulate EMT. In the present study, we used TGF-β1 to induce EMT and aimed to evaluate the effect of resveratrol on EMT and to explore the underline mechanism in GBM. Western blotting was used to detect the expression of EMT-related markers, stemness markers, and Smad-dependent signaling. Wound healing assay and transwell invasion assay were performed to evaluate the migratory and invasive ability of GBM cells. Gliosphere formation assay was used to investigate the effect of resveratrol on the ability of self-renewal. Xenograft experiment was conducted to examine the effect of resveratrol on EMT and Smad-dependent signaling in vivo. Our data validated that resveratrol suppressed EMT and EMT-associated migratory and invasive ability via Smad-dependent signaling in GBM cells. We also confirmed that resveratrol obviously inhibited EMT-induced self-renewal ability of glioma stem cells (GSCs) and inhibited EMT-induced cancer stem cell markers Bmi1 and Sox2, suggesting that resveratrol is able to suppress EMT-generated stem cell-like properties in GBM cells. Furthermore, we also showed the inhibitory effect of resveratrol on EMT in xenograft experiments in vivo. Overall, our study reveals that resveratrol suppresses EMT and EMT-generated stem cell-like properties in GBM by regulating Smad-dependent signaling and provides experimental evidence of resveratrol for GBM treatment.
Highlights
Glioblastoma is the most aggressive solid tumor and the most common primary brain tumor in humans [1]
We first examined the effect of TGF-β1 on cell viability in LN18 and U87 GBM cells in order to exclude the influence of proliferation (Figure 1(a))
We discovered that TGF-β1 had almost no influence on cell viability
Summary
Glioblastoma is the most aggressive solid tumor and the most common primary brain tumor in humans [1]. The standard therapy for newly diagnosed glioblastoma is surgical resection in combination with radiotherapy and chemotherapy [2]. An important property of GBM is that GBM cells tend to infiltrate and invade the surrounding normal brain tissue [4]. This invasive phenotype may lead to the difficulty of complete resection of GBM and recurrence after operation, which is the main cause of treatment failure [5]. It is very important for us to understand this invasive phenotype of GBM, which would be beneficial for the development of more sufficient therapeutic methods targeting GBM
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