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DDTC-Cu(I) inhibits human osteosarcoma cells growth by repressing MET/PI3K/AKT signaling pathway

Ruhao Zhou1,2, Lei Yan1,2, Kun Zhang1,2

  • 1Second Clinical Medical College, Shanxi Medical University, 382 Wuyi Road, Taiyuan, 030001, Shanxi, People's Republic of China.

Scientific Reports
|July 2, 2025
PubMed

Insights

Disulfiram-copper (DDTC-Cu(I)) effectively combats osteosarcoma (OS) by inducing apoptosis and inhibiting cancer cell growth, migration, and invasion. This novel therapeutic shows promise for treating this aggressive bone cancer with minimal side effects.

Area of Science:

  • Oncology
  • Pharmacology
  • Biochemistry

Background:

  • Osteosarcoma (OS) is a primary bone cancer with high metastatic potential and mortality.
  • Disulfiram (DSF), used for alcohol dependency, forms DDTC-Cu(I) in vivo, exhibiting antitumor properties.

Purpose of the Study:

  • To investigate the efficacy of DDTC-Cu(I) against OS cells in vitro and in vivo.
  • To elucidate the underlying molecular mechanisms, focusing on MET and PI3K/AKT signaling pathways.

Main Methods:

  • In vitro studies utilized OS cell lines (U2OS, SaOS2, MG-63) with assays including CCK-8, colony formation, RTCA, transwell invasion, flow cytometry, wound healing, and RNA sequencing.
  • In vivo efficacy was confirmed using a SaOS2 xenograft mouse model with histological analysis of major organs.

Main Results:

  • DDTC-Cu(I) dose-dependently induced apoptosis and suppressed proliferation, migration, and invasion in OS cells.
  • The drug targeted the MET and PI3K/AKT signaling pathways; MET overexpression partially reversed DDTC-Cu(I)'s effects.
  • In vivo studies confirmed DDTC-Cu(I)'s anti-OS efficacy via MET inhibition without significant adverse effects on major organs.

Conclusions:

  • DDTC-Cu(I) demonstrates significant potential as an anti-osteosarcoma therapeutic agent.
  • Targeting MET and PI3K/AKT pathways is crucial for DDTC-Cu(I)'s anti-OS activity.
  • DDTC-Cu(I) presents a promising, safe therapeutic option for osteosarcoma treatment.
Keywords:
DDTC-Cu(I)DisulfiramMET/PI3K/Akt signaling pathwayOsteosarcomaRNA seq

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