Involvement Of Drp1in Hypoxia-induced Migration Of Human Glioblastoma U251Cells

Glioblastoma is the most aggressive brain tumors with high morbidity andmortality. Hypoxia is often the common characteristic of tumor microenvironment,and hypoxia-inducible factor HIF-1α is an essential factor regulating the migratoryactivity of cancer cells including glioblastoma. Recently, mitochondrial dynamics wasfound to be involved in the aggression of cancer cells. However, whether Drp1contributes to the migration of human glioblastoma cells under hypoxia is stillunknown. In the present study, hypoxia was found to up-regulate the transcription andexpression of Drp1, and stimulated mitochondrial fission in glioblastoma U251cells.Inhibition of HIF-1α with Echinomycin blocked hypoxia-induced expression of Drp1.Notably, Drp1inhibitor Mdivi-1efficiently attenuated hypoxia-induced mitochondrialfission and migration of U251cells. In addition, three U251stable cell linesexpressing GFP, GFP-Drp1and dominant negative GFP-Drp1-K38A were establishedto examine the direct role of Drp1in hypoxia-induced migration. MTT assay showedthat there was no significant difference in proliferation of three cell lines. Comparedwith GFP cell line, exogenously expressed GFP-Drp1-K38A inhibitedhypoxia-induced migration of U251cells, while stable expression of GFP-Drp1enhanced the migration of U251cells under hypoxia. Therefore, this study indicatesthe involvement of Drp1in hypoxia-induced migration of human glioblastoma U251cells, and suggests Drp1to be a potential therapeutic target to suppress the aggressionof glioblastoma in the future.