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Avermectin B1 mediates antitumor activity and induces autophagy in osteosarcoma through the AMPK/ULK1 signaling

Xiang Fei1, Zhaohui Li1, Zhen Pan2

  • 1Department of Orthopedics, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 600, Yishan Road, Shanghai, 200233, China.

Cancer Chemotherapy and Pharmacology
|September 5, 2024
PubMed
Abstract

Insights

Avermectin B1 shows promise in treating osteosarcoma by inhibiting cancer cell growth and metastasis. This novel agent activates the AMPK/ULK1 pathway, offering a potential new therapeutic strategy for this challenging bone cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osteosarcoma is a prevalent pediatric bone cancer with limited treatment options.
  • Conventional chemotherapy faces challenges due to drug resistance and toxicity.
  • Novel therapeutic agents are crucial for advanced osteosarcoma management.

Purpose of the Study:

  • To evaluate the anticancer efficacy of avermectin B1 against osteosarcoma cells.
  • To investigate the underlying molecular mechanisms, focusing on the AMPK/ULK1 pathway.
  • To assess the in vivo therapeutic potential of avermectin B1 in a mouse model.

Main Methods:

  • Assessed avermectin B1's half-inhibitory concentration in osteosarcoma cell lines.
  • Conducted functional assays for proliferation, cell cycle, apoptosis, and autophagy.
  • Utilized Western blot to analyze the AMPK/ULK1 signaling pathway.
  • Investigated in vivo tumor growth and metastasis in a xenograft mouse model.
  • Employed an AMPK inhibitor (dorsomorphin) to elucidate pathway involvement.

Main Results:

  • Avermectin B1 dose-dependently inhibited osteosarcoma cell proliferation, migration, and invasion.
  • The compound induced significant apoptosis and autophagy in cancer cells.
  • In vivo studies demonstrated suppression of tumor growth and pulmonary metastasis.
  • Avermectin B1 activated the AMPK/ULK1 pathway, contributing to its antitumor effects.
  • Inhibition of AMPK attenuated avermectin B1's therapeutic activity.

Conclusions:

  • Avermectin B1 exhibits potent anticancer activity against osteosarcoma.
  • The AMPK/ULK1 signaling pathway is a key mediator of avermectin B1's effects.
  • Avermectin B1 represents a potential novel therapeutic agent for osteosarcoma treatment.
Keywords:
AMPK/ULK1 pathwayApoptosisAutophagyAvermectin B1Osteosarcoma

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