Doxorubicin Induces Cytotoxicity through Upregulation of pERK-Dependent ATF3

摘要: Although doxorubicin is commonly used in the treatment of many cancer types, its use chemotherapy has been limited, largely because severe side effects, including cardiotoxicity and nephrotoxicity. In this study, we aimed to identify mechanism doxorubicin-induced cytotoxicity by using human kidney proximal tubule cell line HK-2. Furthermore, investigated role activating transcription factor 3 (ATF3) as a mediator wild-type mouse embryonic fibroblasts (MEF) cells ATF3 knockout (KO) cells. HK-2 cells, decreased viability dose-dependent manner induced an increase sub G1 G2/M phases at all doses. Doxorubicin showed following effects: secretion tumor necrosis alpha; decrease expression phosphorylated protein kinase A Bcl-2; signal transducer activator 3, extracellular signal-regulated (ERK), ATF3. Based on these results, suggest that induces through ERK-dependent pathway, plays pivotal transcriptional regulator process.