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

Author:

Ma Xiaoping12,Chang Junli12,Sun Xingyuan12,Zhou Chujie12,Zhao Peng12,Yang Yanping12

Affiliation:

1. Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China

2. Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, 200032, China

Abstract

Background: Osteosarcoma is the most common primary bone cancer in children and adolescents with high metastatic ability. Aim: 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. Methods: 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. Results: Taken together, our study has demonstrated HCPT to inhibit osteosarcoma growth and metastasis potentially by activating the HIPPO signaling pathway and reversing EMT. Conclusion: HCPT might be a candidate agent for the prevention and treatment of osteosarcoma

Funder

National Nature Science Foundation

National Key R&D Program of China

Shanghai Top Priority Research Center construction project

Shanghai University of Traditional Chinese Medicine

Publisher

Bentham Science Publishers Ltd.

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