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Autophagy inhibition enhances celecoxib-induced apoptosis in osteosarcoma

Pingting Zhou1, Yanyan Li1, Bo Li2

  • 1a Department of Radiation Oncology , Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine , Shanghai , China.

Cell Cycle (Georgetown, Tex.)
|June 10, 2018
PubMed

Insights

Celecoxib, a COX-2 inhibitor, demonstrates significant antitumor effects against osteosarcoma (OS) by inhibiting cell growth and promoting apoptosis. Combining celecoxib with autophagy inhibitors further enhances its effectiveness in treating this aggressive bone cancer.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Osteosarcoma (OS) is a prevalent and aggressive bone cancer in children and adolescents, characterized by early metastasis.
  • Effective therapeutic strategies for OS remain a critical unmet need.

Purpose of the Study:

  • To investigate the antitumor activity and underlying mechanisms of celecoxib, a selective COX-2 inhibitor, in osteosarcoma.
  • To evaluate the potential synergistic effects of combining celecoxib with autophagy inhibitors.

Main Methods:

  • In vitro studies using OS cell lines (143B, U2OS) treated with celecoxib.
  • Assessment of cell viability, cell cycle progression, apoptosis, mitochondrial pathways, and migration.
  • In vivo studies using OS tumor xenografts.
  • Combination treatments with autophagy inhibitors (CQ, SAR405) and genetic inhibition (shRNA targeting Atg5).

Main Results:

  • Celecoxib exhibited dose-dependent inhibition of OS cell growth, G0/G1-phase arrest, and reduced migration.
  • Celecoxib induced apoptosis via the mitochondrial pathway.
  • Combination therapy with autophagy inhibitors (CQ, SAR405) or Atg5 knockdown significantly enhanced celecoxib's antiproliferative and pro-apoptotic effects.
  • Celecoxib demonstrated antitumor activity in vivo xenograft models.

Conclusions:

  • Celecoxib possesses significant antitumor activity against osteosarcoma.
  • The combination of celecoxib with autophagy inhibition presents a promising therapeutic strategy for osteosarcoma treatment.
  • Understanding these mechanisms provides insights for developing novel therapeutic approaches for OS patients.
Keywords:
Celecoxibapoptosisautophagyosteosarcoma

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