(S)-10-羟基喜树碱通过激活 Hippo 信号通路抑制 EMT 诱导的骨肉瘤细胞生长和转移。
(S)-10-Hydroxycamptothecin Inhibits EMT-evoked Osteosarcoma Cell Growth and Metastasis by Activating the HIPPO Signaling Pathway.
机构信息
Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, 200032, China.
出版信息
Comb Chem High Throughput Screen. 2024;27(15):2239-2248. doi: 10.2174/0113862073263020231220043405.
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.
背景
骨肉瘤是儿童和青少年中最常见的原发性骨癌，具有高转移能力。
目的
本研究旨在探讨（S）-10-羟基喜树碱（HCPT）对骨肉瘤细胞生长和转移的抑制作用及其机制。
方法
用 HCPT（20、100 或 300 nM）处理骨肉瘤细胞 143B 和 U-2 OS（U-2），进行 CCK-8、流式细胞术、Transwell、划痕愈合和免疫印迹检测。HCPT 暴露的 143B 和 U-2 细胞中 EMT 相关关键蛋白 N-钙粘蛋白、Snail 和波形蛋白下调，E-钙粘蛋白呈剂量依赖性上调。此外，143B 和 U-2 细胞与 HCPT 孵育 3 小时呈剂量依赖性降低 p-LATS1/LATS1、p-MST1/MST1、p-YAP/YAP 和 p-TAZ/TAZ 的表达比值。
结果
综上所述，我们的研究表明 HCPT 通过激活 HIPPO 信号通路和逆转 EMT 来抑制骨肉瘤的生长和转移。
结论
HCPT 可能是预防和治疗骨肉瘤的候选药物。
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