Dorsomorphin Suppresses EMT to Reduce AR-Negative Prostate Cancer Metastasis by Synergistically Antagonizing

Related Experiment Video

Updated: Jan 15, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
06:48

An Orthotopic Murine Model of Human Prostate Cancer Metastasis

Published on: September 18, 2013

35.8K

Dongzhang Li1, Guantao Lou1, Wei Tian1

  • 1Department of Urology, Shaoxing Central Hospital, Shaoxing 312030, China.

Prostate Cancer
|October 9, 2025
PubMed

Insights

Dorsomorphin, an AMPK inhibitor, effectively inhibits prostate cancer cell invasion and metastasis. It works by suppressing key signaling pathways involved in epithelial-mesenchymal transition and angiogenesis, offering a potential new therapeutic strategy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Prostate cancer is a prevalent male reproductive system tumor with limited effective treatments.
  • AMPK inhibitor dorsomorphin shows potential antitumor effects, but its mechanism in prostate cancer is unknown.
  • Understanding dorsomorphin's molecular targets is crucial for developing new prostate cancer therapies.

Purpose of the Study:

  • To investigate the effects of dorsomorphin on prostate cancer cell invasion, infiltration, epithelial-mesenchymal transition (EMT), and angiogenesis.
  • To elucidate the molecular mechanisms underlying dorsomorphin's anti-prostate cancer activity.
  • To evaluate dorsomorphin's antitumor and antimetastatic potential in vitro and in vivo.

Main Methods:

  • In vitro assays using DU145 and PC-3 prostate cancer cell lines to assess invasion, infiltration, and EMT.
  • Analysis of extracellular matrix components and angiogenesis-related proteins (HIF-1α, VEGF).
  • Nude mouse tumorigenic experiments to confirm antitumor effects; investigation of TGF-β1, Smad2/3, JAK2/STAT3, and Shh signaling pathways.

Main Results:

  • Dorsomorphin significantly inhibited prostate cancer cell invasion and infiltration in a dose- and time-dependent manner.
  • Dorsomorphin reduced expression of extracellular matrix components and angiogenesis factors (HIF-1α, VEGF), and antagonized EMT.
  • Mechanistically, dorsomorphin suppressed TGF-β1, inhibited Smad2/3 signaling, and inactivated JAK2/STAT3 and Gli2-independent Shh pathways.

Conclusions:

  • Dorsomorphin exhibits significant antitumor and antimetastatic effects against prostate cancer.
  • The mechanism involves synergistic antagonism of JAK2/STAT3 and Gli2-independent Shh signaling, inhibiting TGF-β1-mediated EMT.
  • Dorsomorphin represents a promising therapeutic agent for prostate cancer, targeting key metastatic pathways.
Keywords:
JAK2/STAT3TGF-β1/Smad2/3dorsomorphinepithelial-mesenchymal transition (EMT)prostate cancersonic hedgehog

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