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TGF‑β inhibitor RepSox suppresses osteosarcoma via the JNK/Smad3 signaling pathway

Dengwei He1, Jiawei Gao1, Lin Zheng1

  • 1Department of Orthopedics, Affiliated Lishui Hospital of Zhejiang University, Lishui, Zhejiang 323000, P.R. China.

International Journal of Oncology
|September 17, 2021
PubMed

Insights

RepSox, a transforming growth factor-β (TGF-β) inhibitor, effectively suppresses osteosarcoma (OS) progression by inhibiting cell proliferation, migration, and epithelial-mesenchymal transition (EMT). This study highlights RepSox as a potential therapeutic agent for osteosarcoma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osteosarcoma (OS) is the most common primary bone malignancy with poor long-term survival rates.
  • Transforming growth factor-β (TGF-β) signaling is implicated in OS progression.
  • RepSox is a known inhibitor of TGF-β signaling.

Purpose of the Study:

  • To investigate the anti-cancer effects of RepSox on osteosarcoma cells.
  • To elucidate the molecular mechanisms underlying RepSox's action in OS.
  • To evaluate RepSox's therapeutic potential for osteosarcoma.

Main Methods:

  • In vitro studies using OS cell lines (HOS, 143B) to assess proliferation, apoptosis, migration, and invasion.
  • Western blotting to analyze protein expression related to epithelial-mesenchymal transition (EMT) and signaling pathways (JNK, Smad3).
  • In vivo xenograft mouse model to evaluate tumor growth inhibition.

Main Results:

  • RepSox significantly inhibited OS cell proliferation by inducing S-phase arrest and apoptosis.
  • RepSox suppressed OS cell migration and invasion.
  • RepSox treatment downregulated EMT markers (N-cadherin, Vimentin, MMP-2, MMP-9) and upregulated E-cadherin.
  • RepSox inhibited the JNK and Smad3 signaling pathways.
  • RepSox demonstrated significant tumor growth inhibition in a xenograft model.

Conclusions:

  • RepSox exhibits potent anti-osteosarcoma activity by inhibiting proliferation, EMT, and promoting apoptosis.
  • The anti-cancer effects of RepSox are mediated through the inhibition of JNK/Smad3 signaling pathways.
  • RepSox represents a promising therapeutic candidate for osteosarcoma treatment.
Keywords:
JNK/Smad3RepSoxosteosarcomatherapeutictransforming growth factor‑β

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