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Updated: Jul 3, 2026

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
04:25

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models

Published on: October 28, 2021

LL-37 inhibits osteosarcoma progression by suppressing SQLE-mediated cholesterol synthesis via the PTEN/AKT/mTOR

Fatai Lu1,2, Zhijun Liu2, Huasheng Jiang2

  • 1Department of Clinical Epidemiology and Evidence-Based Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.

Journal of Bone Oncology
|July 2, 2026
PubMed

Insights

The human cathelicidin peptide LL-37 effectively inhibits osteosarcoma (OS) growth by targeting cholesterol synthesis and inducing cell death. This peptide shows promise as a novel therapeutic strategy for OS, offering a new avenue for targeted treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Osteosarcoma (OS) is an aggressive bone cancer with limited treatment options for advanced cases.
  • The anti-tumor potential of the human cathelicidin peptide LL-37 in OS is largely unexplored.
  • There is a critical need for novel therapeutic strategies to combat OS.

Purpose of the Study:

  • To investigate the anti-osteosarcoma (OS) activity of the human cathelicidin peptide LL-37.
  • To elucidate the underlying molecular mechanisms of LL-37's anti-OS effects.
  • To evaluate LL-37 as a potential therapeutic agent for OS.

Main Methods:

  • In vitro studies using OS cell lines and mesenchymal stem cells (hBMSCs) assessed cell viability, migration, invasion, cell cycle, and cell death.
  • Transcriptomic profiling, gene knockdown/overexpression, and rescue experiments identified key signaling pathways.
  • In vivo efficacy was evaluated using an OS xenograft mouse model.

Main Results:

  • LL-37 selectively reduced OS cell viability and suppressed migration and invasion, with minimal toxicity to hBMSCs.
  • LL-37 induced S-phase arrest and triggered both apoptosis and pyroptosis, linked to the caspase-1/GSDMD pathway.
  • LL-37 downregulated cholesterol biosynthesis by inhibiting SREBP2/SQLE, mediated by PTEN/AKT/mTOR pathway activation. In vivo, LL-37 inhibited tumor growth effectively.

Conclusions:

  • LL-37 exhibits potent anti-osteosarcoma activity by targeting the PTEN/AKT/mTOR-SREBP2/SQLE axis to inhibit cholesterol synthesis and induce dual cell death.
  • LL-37 demonstrates selective efficacy and provides a theoretical basis for developing cholesterol metabolism-targeted therapies for osteosarcoma.
  • LL-37 represents a promising candidate for novel osteosarcoma treatment strategies.
Keywords:
ApoptosisCholesterol metabolismLL-37OsteosarcomaPTEN/AKT/mTOR pathwayPyroptosisSQLE

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