Mitochondrial Dysfunctions Regulated Radioresistance through Mitochondria-to-Nucleus Retrograde Signaling Pathway of NF-κB/PI3K/AKT2/mTOR

Radioresistance Radiosensitivity
DOI: 10.1667/rr15021.1 Publication Date: 2018-06-04T13:10:33Z
ABSTRACT
We investigated the relationship between significantly different genes of mitochondria-to-nucleus retrograde signaling pathway (RTG) in H1299 ρ0 cells (mtDNA depleted cell) and compared their radiosensitivity to that parental ρ cells, determine possible intervention targets radiosensitization. were mitochondrial DNA by chronic culturing ethidium bromide at low concentration. Radiosensitivity was analyzed using clonogenic assay. Western blot used analyze cell cycle-related proteins, serine/threonine kinase ataxia telangiectasia mutant (ATM), Rad3-related protein (ATR) cyclin B1 (CCNB1). The γ-H2AX foci detected confocal fluorescence microscopy. RNA samples hybridized Agilent human genome expression microarray. Kyoto Encyclopedia Genes Genomes (KEGG) database for Gene Ontology (GO) Consortium annotations differentially expressed genes, respectively. found be more radioresistant than cells. ATP production lower before or after irradiation. Both had higher ROS levels irradiation, however, radiation-induced In addition, percentage apoptosis 6 Gy As cycle damage response-related proteins ATM, ATR CCNB1, there less Furthermore, results microarray demonstrated phosphorylated NF-κB/PI3K/AKT2/mTOR increased irradiation decreased treatment with AKT2-specific inhibitor MK-2206 combined radiation also led an increase pro-apoptotic proteins. conclusion, these demonstrate mtDNA depletion might activate induce radioresistance evoking dysfunctions.
SUPPLEMENTAL MATERIAL
Coming soon ....
REFERENCES (56)
CITATIONS (19)