Oleanolic acid inhibits cell proliferation migration and invasion and induces SW579 thyroid cancer cell line apoptosis by targeting forkhead transcription factor A

摘要

Oleanolic acid (OA) is a naturally occurring triterpenoid that possesses antitumor activity against several tumor cell lines. However, the potential mechanism underlying OA-induced thyroid carcinoma cell death is poorly understood. We investigated the biological functions of OA by performing migration, invasion, colony formation, and apoptosis assays on SW579 cells. Forkhead box A1 (FOXA1) expression was used to predict poor prognosis in patients with thyroid carcinoma among the TCGA samples from the UALCAN and gene expression profiling interactive analysis databases. Western blot was used to detect protein expression level. Results revealed that OA inhibited the migration, colony formation, and invasion of thyroid carcinoma cells in a dose-dependent manner. Further investigation verified that OA treatment induced significant apoptosis of thyroid carcinoma cells. Moreover, high FOXA1 expression predicted the poor prognosis of patients with thyroid cancer. The proliferation, migration, and invasion of thyroid carcinoma cells were significantly decreased when FOXA1 was silenced. OA significantly increased Akt phosphorylation and reduced FOXA1 expression in SW579 cells, but only PI3K/Akt inhibitor LY294002 attenuated OA-induced FOXA1 downregulation. Furthermore, Akt overexpression suppressed the FOXA1 expression in SW579 cells. In addition, molecular docking assay revealed that OA possessed high affinity toward FOXA1 with a low binding energy. OA may be a potential chemotherapeutic agent against thyroid carcinoma cells.