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Updated: Oct 21, 2025

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

8.1K

Effect of the Notch1-mediated PI3K-Akt-mTOR pathway in human osteosarcoma

Kexiang Zhang1, Song Wu1, Hongwei Wu2

  • 1Department of Orthopedics, Third Xiangya Hospital, Central South University, Changsha 410013, Hunan Province, China.

Aging
|September 8, 2021
PubMed
Abstract

Insights

Notch1 activation suppresses osteosarcoma cell growth by halting the cell cycle and promoting apoptosis and autophagy. This pathway may offer a new therapeutic target for osteosarcoma treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Osteosarcoma is a prevalent adolescent bone cancer with stagnant incidence rates, necessitating novel therapeutic strategies.
  • The Notch1 pathway, absent in osteosarcoma cells, is implicated in cancer cell proliferation, apoptosis, and autophagy.
  • Investigating Notch1's role is crucial for understanding and potentially treating osteosarcoma.

Purpose of the Study:

  • To investigate the role of Notch1 activation in osteosarcoma development.
  • To determine the effects of Notch1 on osteosarcoma cell proliferation, cell cycle, apoptosis, and autophagy.
  • To elucidate the molecular mechanisms underlying Notch1's action in osteosarcoma.

Main Methods:

  • Doxycycline was used to induce Notch1 activation (NICD1 expression) in human osteosarcoma cells (MG-63).
  • Cell viability, cell cycle progression (via flow cytometry), apoptosis, and autophagy (via GFP-LC3 plasmid) were assessed.
  • Western blotting was employed to analyze the PI3K/Akt/mTOR signaling pathway.

Main Results:

  • Notch1 activation by doxycycline significantly suppressed osteosarcoma cell proliferation by inducing S phase arrest.
  • Doxycycline-induced Notch1 activation triggered apoptosis and autophagy in osteosarcoma cells.
  • Notch1 was found to inhibit the PI3K/Akt/mTOR signaling pathway, mediating apoptosis and autophagy.

Conclusions:

  • Notch1 activation induces S phase arrest, apoptosis, and autophagy in human osteosarcoma cells by inhibiting the PI3K/Akt/mTOR pathway.
  • Notch1 represents a potential clinical antitumour target for osteosarcoma therapy.
Keywords:
Notch1PI3K/Akt/mTORautophagyosteosarcoma

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