FOXO3a protects glioma cells against temozolomide-induced DNA double strand breaks via promotion of BNIP3-mediated mitophagy

摘要: FOXO3a (forkhead box transcription factor 3a) is involved in regulating multiple biological processes cancer cells. BNIP3 (Bcl-2/adenovirus E1B 19-kDa-interacting protein 3) a receptor accounting for priming damaged mitochondria autophagic removal. In this study we investigated the role of sensitivity glioma cells to temozolomide (TMZ) and its relationship with BNIP3-mediated mitophagy. We showed that TMZ dosage-dependently inhibited viability human U87, U251, T98G, LN18 rat C6 IC50 values 135.75, 128.26, 142.65, 155.73 111.60 μM, respectively. U87 U251 cells, (200 μM) induced DNA double strand breaks (DSBs) nuclear translocation apoptosis inducing (AIF), which was accompanied by mitophagy accumulation nucleus. treatment intracellular ROS via enhancing mitochondrial superoxide, not only contributed DSBs exacerbated dysfunction, but also upregulated expression. Knockdown aggravated TMZ-induced damage, as well cell death. activated autophagy, triggered prompting reinforcing interaction LC3BII. Inhibition knocking down SiRNA or blocking autophagy 3MA bafilomycin A1 superoxide accumulation. Moreover, knockdown upregulation activation. addition, (100 mg·kg-1·d-1, ip) 12 days xenograft mice markedly tumor growth upregulation, oxidative stress tissues. These results demonstrate attenuates temozolomide-induced promoting