Decitabine-Induced Changes in Human Myelodysplastic Syndrome Cell Line SKM-1 Are Mediated by FOXO3A Activation
BACKGROUND Sunitinib (SUN), a tyrosine kinase inhibitor, is a promising treatment for triple-negative breast cancer (TNBC), the most aggressive and fast-growing type of breast cancer. Yet, the protective effect of SUN against TNBC is poorly investigated and the role of Forkhead box type O (FOXO3a) transcription factor is still unknown. MATERIALS AND METHODS Cell proliferation was evaluated using the MTT assay. The mRNA and protein expression of apoptotic, oxidative stress and cell cycle genes were determined by real-time polymerase chain reaction (RT-PCR) and western blot analyses, respectively. Percentage of the apoptotic cells were determined by flow cytometry. The role of FOXO3a was knock-downed using siRNA. RESULTS SUN caused suppression of MDA-MB231 cell growth associated with induction of apoptosis, cell cycle arrest, oxidative stress markers and FOXO3a gene. Importantly, silencing of FOXO3a mRNA using siRNA significantly rescued MDA-MB231 cells from SUN-induced cell-proliferative arrest. CONCLUSION SUN inhibits TNBC MDA-MB231 cell proliferation through activation of FOXO3a expression.