Downregulation of CUEDC2 prevents doxorubicin‑induced cardiotoxicity in H9c2 cells.

Abstract

Treatment with doxorubicin (DOX), which is an effective anticancer agent, is limited by cardiotoxicity. CUE domain-containing 2 (CUEDC2) serves a role in numerous cellular processes. The present study aimed to elucidate the potential function of CUEDC2 in DOX-induced cardiotoxicity. Cell Counting kit-8 assay demonstrated that DOX induced cytotoxicity of H9c2 cells in a dose-dependent manner. Flow cytometry demonstrated that downregulation of CUEDC2 reduced the levels of DOX-induced reactive oxygen species. Furthermore, compared with in the DOX-treated group, the activity of superoxide dismutase was increased in the DOX + small interfering RNA (si)CUEDC2 group; whereas, the malondialdehyde content was reduced in the DOX + siCUEDC2 group. In addition, flow cytometric analysis indicated that mitochondrial membrane potential was maintained following the depletion of CUEDC2. Furthermore, CUEDC2 downregulation significantly inhibited DOX-induced apoptosis. The expression levels of proapoptotic genes, including B-cell lymphoma 2 (Bcl-2)-associated X protein, cleaved caspase-3 and cytochrome c were inhibited by the depletion of CUEDC2. Conversely, the expression levels of the anti-apoptotic gene Bcl-2 were elevated in the CUEDC2 knockdown group. Downregulation of CUEDC2 also increased phosphorylation of protein kinase B and forkhead box O3a, and decreased the expression of Bcl-2-like protein 11 according to western blot analysis. Taken together, the present study demonstrated that CUEDC2 downregulation prevented DOX-induced cardiotoxicity in H9c2 cells. Therefore, CUEDC2 may be a promising target for the prevention of DOX-induced cardiotoxicity.