Oleanolic acid inhibits osteosarcoma cell proliferation and invasion by suppressing the SOX9/Wnt1 signaling pathway

Exp Ther Med. 2021 May;21(5):443. doi: 10.3892/etm.2021.9883. Epub 2021 Feb 28.

ABSTRACT

Osteosarcoma is the most common primary bone malignancy in children and adolescents. Inhibition of SOX9/Wnt1-mediated signaling might suppress osteosarcoma metastasis, and oleanolic acid (OA) might decrease the activity of the SOX9/Wnt1 signaling pathway. The aim of the present study was to determine the role of OA in osteosarcoma cell proliferation and invasion. Osteosarcoma cell lines (KHOS and U2OS) and an osteoblastic cell line (hFOB1.19) were used for cell viability, proliferation and invasion analysis. The data suggested that OA significantly inhibited cell viability on days 3, 4 and 5 compared with the control (Ctrl) group in both U2OS and KHOS cells. Cell proliferation in the OA-treated group was significantly decreased compared with the Ctrl group in the osteosarcoma cell lines. Analysis of the cell cycle indicated that OA significantly reduced the percentage of U2OS and KHOS cells in the S phase compared with the Ctrl group. The wound healing assay results indicated that the OA group displayed significantly decreased cell re-colonization of the wound at 48 h compared with the Ctrl group. The Transwell chamber assay results also indicated that cell invasion was significantly inhibited by OA compared with the Ctrl group. Furthermore, OA significantly increased osteosarcoma cell apoptosis compared with the Ctrl group. Similarly, the protein expression levels of SOX9 and Wnt1 were significantly decreased in OA-treated U2OS and KHOS cells compared with Ctrl cells. OA-mediated downregulation of Wnt1 expression was reversed following SOX9 small interfering RNA transfection. Collectively, the results indicated that OA inhibited SOX9/Wnt1-associated osteosarcoma cell proliferation, migration and invasion.

PMID:33747179 | PMC:PMC7967867 | DOI:10.3892/etm.2021.9883