(S)-10-Hydroxycamptothecin Inhibits EMT-evoked Osteosarcoma Cell Growth and Metastasis by Activating the HIPPO Signaling Pathway.

Abstract

Osteosarcoma is the most common primary bone cancer in children and adolescents with high metastatic ability. This study aimed to explore the inhibitory effects of (S)-10-hydroxycamptothecin (HCPT) on osteosarcoma cell growth and metastasis as well as the underlying mechanism. The osteosarcoma cells of 143B and U-2 OS (U-2), treated with HCPT (20, 100, or 300 nM), underwent detections, such as CCK-8, flow cytometry, Transwell, wound healing, and immunoblotting. EMT-related key proteins, like N-cadherin, Snail, and Vimentin, were found to be down-regulated, while E-cadherin was up-regulated dose-dependently in HCPT-exposed 143B and U-2 cells. Additionally, incubation of 143B and U-2 cells with HCPT for 3 hours dosedependently reduced the expression ratios of p-LATS1/LATS1, p-MST1/MST1, p-YAP/YAP, and p-TAZ/TAZ. Taken together, our study has demonstrated HCPT to inhibit osteosarcoma growth and metastasis potentially by activating the HIPPO signaling pathway and reversing EMT. HCPT might be a candidate agent for the prevention and treatment of osteosarcoma.