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Updated: Feb 26, 2026

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
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Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma

Published on: April 12, 2019

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Dopamine D1 receptors induce apoptosis of osteosarcoma cells via changes of MAPK pathway

Jun Gao1, Feng Gao2

  • 1Department of Orthopeadic Surgery, The First Hospital of Harbin, Harbin, China.

Clinical and Experimental Pharmacology & Physiology
|July 13, 2017
PubMed

Insights

Dopamine D1 receptor (DR1) activation triggers apoptosis in osteosarcoma cells by influencing the MAPK pathway. This research highlights DR1 as a potential target for osteosarcoma treatment.

Area of Science:

  • Oncology
  • Neuropharmacology
  • Cell Biology

Background:

  • Osteosarcoma is a primary bone malignancy with limited treatment options.
  • Dopamine receptors, particularly the dopamine D1 receptor (DR1), are implicated in various cellular processes.
  • The role of DR1 in osteosarcoma cell apoptosis remains largely unexplored.

Discussion:

  • Activation of DR1 using the agonist SKF-38393 significantly reduced osteosarcoma cell viability and induced apoptosis.
  • The DR1 antagonist SCH-23390 counteracted the pro-apoptotic effects of SKF-38393, confirming DR1's specific role.
  • Overexpression of DR1 in osteosarcoma cells promoted apoptosis, evidenced by increased caspase-9 and -3 activity and cytochrome c release.

Key Insights:

  • DR1 activation modulates apoptosis-related proteins, decreasing the anti-apoptotic Bcl-2 and increasing pro-apoptotic factors.
  • DR1 signaling influences the mitogen-activated protein kinase (MAPK) pathway, specifically inhibiting ERK1/2 phosphorylation while activating p38 MAPK and JNK.
  • These findings establish a mechanistic link between DR1 activation and the induction of osteosarcoma cell death via the MAPK cascade.

Outlook:

  • DR1 emerges as a potential therapeutic target for osteosarcoma.
  • Further investigation into DR1-targeted therapies could lead to novel treatment strategies.
  • Understanding the intricate signaling network involving DR1 and MAPK pathways may reveal synergistic therapeutic approaches.
Keywords:
MAPK pathwayapoptosisdopamine D1 receptorsosteosarcoma cells

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