Zhou Ruhao, Yan Lei, Zhang Kun, Chen Song, Yu Yang, Wei Xiaochun, Pan Yongchun, Xu Chaojian, Sun Xiaojuan, Lv Zhi, Li Pengcui, Qiao Xiaochen, Feng Yi, Tian Zhi
Second Clinical Medical College, Shanxi Medical University, 382 Wuyi Road, Taiyuan, 030001, Shanxi, People's Republic of China.
Department of Orthopedics, Shanxi Key laboratory of Bone and Soft Tissue Injury Repair, The Second Hospital of Shanxi Medical University, 382 Wuyi Road, Taiyuan, 030001, Shanxi, People's Republic of China.
Sci Rep. 2025 Jul 1;15(1):21780. doi: 10.1038/s41598-025-06748-6.
Osteosarcoma (OS) is a frequently occurring bone malignancy with increased metastatic properties, causing deaths in large numbers around the world. Disulfiram (DSF) is clinically utilized to treat alcohol dependency and has been indicated to bind Cu(I) in-vivo to form DDTC-Cu(I), which has been confirmed for its antitumor effects. This investigation aimed to elucidate the efficacy of DDTC-Cu(I) on OS cell apoptosis, migration, growth, invasion, and underlying mechanisms. The in-vitro investigations were performed on U2OS, SaOS2, and MG-63 OS cell lines and included CCK-8, colony formation, RTCA, transwell invasion, flow cytometry, wound healing, and RNA seq assays. DDTC-Cu(I) was inoculated dose-dependent, increased apoptosis, and suppressed cells' ability to proliferate, migrate, and invade via the MET and PI3K/AKT signaling pathways. Additionally, MET's overexpression partially reversed the anti-OS and PI3K/AKT signaling pathways suppression effect of DDTC-Cu(I). Furthermore, the SaOS2 xenograft mice model was utilized to confirm the in-vivo anti-OS efficacy of DDTC-Cu(I) by MET protein inhibition. The histological research revealed that DDTC-Cu(I) had no adverse influence on the liver, heart, lungs, and kidneys. Overall, the data of this investigation suggested that DDTC-Cu(I) could serve as an efficient agent against OS development.
骨肉瘤（OS）是一种常见的具有高转移特性的骨恶性肿瘤，在全球导致大量死亡。双硫仑（DSF）在临床上用于治疗酒精依赖，并且已表明其在体内与Cu（I）结合形成二乙胺基二硫代甲酸盐-Cu（I）（DDTC-Cu（I）），其抗肿瘤作用已得到证实。本研究旨在阐明DDTC-Cu（I）对OS细胞凋亡、迁移、生长、侵袭的影响及其潜在机制。体外实验在U2OS、SaOS2和MG-63骨肉瘤细胞系上进行，包括CCK-8、集落形成、实时细胞分析、Transwell侵袭、流式细胞术、伤口愈合和RNA测序分析。DDTC-Cu（I）呈剂量依赖性接种，增加细胞凋亡，并通过MET和PI3K/AKT信号通路抑制细胞增殖、迁移和侵袭能力。此外，MET的过表达部分逆转了DDTC-Cu（I）对骨肉瘤及PI3K/AKT信号通路的抑制作用。此外，利用SaOS2异种移植小鼠模型通过抑制MET蛋白来证实DDTC-Cu（I）在体内的抗骨肉瘤疗效。组织学研究表明，DDTC-Cu（I）对肝脏、心脏、肺和肾脏没有不良影响。总体而言，本研究数据表明，DDTC-Cu（I）可作为一种有效的抗骨肉瘤药物。
