FoxO3a is essential for the antiproliferative and apoptogenic effects of sunitinib in MDA-MB231 cell line

Abstract

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 realtime 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.