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1.
Environ Toxicol Pharmacol ; 80: 103439, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32585423

RESUMO

To investigate the effects of quercetin on cell viability and apoptosis in meningioma cells and to determine the underlying molecular mechanism. HBL-52 meningioma cells were treated with quercetin at doses of 1, 5, 10, 20, and 40 ng/mL for 24, 36 and 48 h, and cell viability was assessed using the Cell Counting kit-8 (CCK-8) test. Apoptosis was determined by flow cytometry. Bax, Bcl-2, and IGFBP5 protein expression was assessed by western blot, and IGFBP5 and miR-197 mRNA levels were measured using quantitative reverse transcription PCR (qRT-PCR). The interaction between miR-197 and IGFBP5 was verified by dual luciferase assay. Quercetin reduces viability and proliferation and increases apoptosis in HBL-52 cells in a dose- and time-dependent manner. Quercetin treatment also decreases Bcl-2 and increases Bax protein expression, and increases miR-197 mRNA while reducing IGFBP5 mRNA expression. A dual luciferase assay showed that miR-197 interacts directly with binding sites in the 3'untranslated region of IGFBP5, and that miR-197 overexpression reduced IGFBP5 expression. Quercetin may reduce meningioma cell proliferation and increase apoptosis by activating the miR-197/IGFBP5 cascade and regulating Bcl-2/Bax.


Assuntos
Apoptose/efeitos dos fármacos , Proteína 5 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Neoplasias Meníngeas/patologia , Meningioma/patologia , MicroRNAs/genética , Quercetina/farmacologia , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Neoplasias Meníngeas/genética , Meningioma/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
2.
Onco Targets Ther ; 12: 11579-11586, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31920345

RESUMO

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 3'UTR 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 3'UTR 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.

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