Objective: To investigate the effects of resveratrol on apoptosis and proliferation in meningioma cells and characterize the underlying molecular mechanism.
Methods: HBL-52 meningioma cells were treated with resveratrol at doses of 10, 50, 100, 200, and 400 μM for 24, 36, and 48 hrs. Inhibition of proliferation was measured by CCK8 assay, and apoptosis was determined by annexin V staining and flow cytometry. Expression of apoptosis-associated proteins (cleaved-caspase-3, pro-caspase-3) and Bcl-2 were measured by Western blot. Levels of miR-34a-3p and Bcl-2 mRNA were analyzed by reverse transcriptase PCR. A dual luciferase assay was used to determine whether miR-34a-3p binds to the 3ʹUTR of Bcl-2.
Results: Resveratrol reduces proliferation and increases apoptosis in HBL-52 cells. These effects increase with increasing resveratrol concentration and exposure time. Resveratrol increases levels of cleaved-caspase 3 protein as well as decreases levels of pro-caspase 3 protein and Bcl-2 mRNA. The 3ʹUTR of Bcl-2 contains putative binding sites for miR-34a-3p, and these binding sites can regulate the expression of a luciferase reporter. Overexpression of miR-34a-3p reduces Bcl-2 protein levels in HBL-52 cells.
Conclusion: Resveratrol suppresses proliferation and induces apoptosis in meningioma cells by upregulating miR-34a-3p, which in turn downregulates Bcl-2. Resveratrol may be a useful drug for treating meningiomas.
Keywords: resveratrol, meningioma, miR-34a-3p, apoptosis