- Journal of Basic and Clinical Health Sciences
- Vol: 4 Issue: 3
- Repositioning of Metformin: Anticancer Agent for Hypoxic Neuroblastoma Cells
Repositioning of Metformin: Anticancer Agent for Hypoxic Neuroblastoma Cells
Authors : Seniz Inanc Surer, Feriha Toksoz, Serdar Bayrak, Hanife Ecenur Meco, Tolga Sever, Yasemin Basbinar, Hatice Nur Olgun
Pages : 384-390
Doi:10.30621/jbachs.2020.1373
View : 21 | Download : 7
Publication Date : 2020-09-01
Article Type : Other
Abstract :Objectives:Neuroblastoma is an extracranial solid tumor of early childhood that has a hypoxic environment. VEGF and HIFs molecules play a role in adaptation to this microenvironment. Hypoxic microenvironment leads to poor prognosis and inadequate treatment of neuroblastoma. Metformin has been shown to inhibit tumor growth, might be a potential chemotherapeutic agent. The anti-cancer activity of Metformin on SH-SY5Y cells are not fully elucidated. The aim of this study is to determine the anti-cancer effect of Metformin on SH-SY5Y cells and to elucidate its molecular action mechanism in hypoxia/normoxia. Patients and Methods:SH-SY5Y cells were exposed to increasing doses of Metformin. The viability of SH-SY5Y cells was evaluated using the real time xCELLigence RTCA system. Migration of SH-SY5Y cells was determined using wound healing. The effect of metformin on mRNA and protein expression levels was evaluated using Real-time PCR and Western Blot, respectively. Results:Metformin was observed to significantly reduce the viability of SH-SY5Y cells. Metformin treatment reduced migration of SH-SY5Y cells. In addition, Metformin treatment significantly reduced mRNA expression of HIF-1α, PDK-1 and VEGF-A in SH-SY5Y cells under normoxia and hypoxia. In hypoxia condition, protein expression of HIF-1α and VEGF-A decreased after Metformin administration on SH-SY5Y cells. Protein expression of PDK-1 was observed to decrease in both normoxia and hypoxia conditions on SH-SY5Y cells. Conclusion:In this study, the anti-cancer effect of Metformin on SH-SY5Y cells was determined. Metformin has been observed as inhibitor of migration in SH-SY5Y. Metformin treatment has been shown to reduce gene and protein levels of HIF-1α and target molecules in neuroblastoma cells.Keywords : neuroblastoma, metformin, hypoxia, HIF-1α, VEGF-A, PDK-1