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Updated: Oct 12, 2025

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ACT001 reverses resistance of prolactinomas via AMPK-mediated EGR1 and mTOR pathways

Junhao Zhu1, Chao Tang1, Zixiang Cong1

  • 1Department of Neurosurgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu Province, China.

Endocrine-Related Cancer
|November 25, 2021
PubMed

Insights

ACT001, a novel compound, effectively reverses dopamine agonist resistance in prolactinoma cells. It targets specific pathways to overcome drug resistance, offering a promising treatment for resistant prolactinomas.

Area of Science:

  • Endocrinology
  • Oncology
  • Pharmacology

Background:

  • Dopamine agonists (DAs) are primary treatments for prolactinomas.
  • Tumor heterogeneity leads to unavoidable drug resistance during DA therapy.
  • Prolactinoma cell lines exhibit varied responses to DAs like cabergoline (CAB) and bromocriptine (BRC).

Purpose of the Study:

  • To investigate ACT001's potential to overcome dopamine agonist resistance in prolactinoma cells.
  • To elucidate the molecular mechanisms by which ACT001 reverses resistance.
  • To evaluate ACT001 as a therapeutic agent for drug-resistant prolactinomas.

Main Methods:

  • Utilized two prolactinoma cell lines (GH3 and MMQ) with differential DA sensitivity.
  • Assessed ACT001's effect on AMPK activation, ROS levels, and AMP/ATP ratio.
  • Analyzed downstream signaling pathways including mTOR, EGR1, autophagy, and apoptosis.

Main Results:

  • ACT001 activated AMPK by increasing intracellular ROS and AMP/ATP ratio.
  • In GH3 cells, ACT001 reversed CAB resistance by inhibiting mTOR signaling and inducing autophagic cell death.
  • In MMQ cells, ACT001 reversed BRC resistance by activating EGR1 signaling and inducing apoptotic cell death.

Conclusions:

  • ACT001 demonstrates dual mechanisms to overcome DA resistance in different prolactinoma contexts.
  • ACT001 shows significant promise as a therapeutic compound for dopamine agonist-resistant prolactinomas.
Keywords:
ACT001AMPKdopamine receptor agonistdrug resistanceprolactinoma

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