Ailanthone targets the EGR3-SOCS2 regulatory pathway to suppress vasculogenic mimicry in prostate cancer

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Prostate cancer (PCa) progression to castration-resistant stages presents poor prognosis.
• Vasculogenic mimicry (VM) is a key factor in PCa aggressiveness and therapeutic resistance.

Purpose of the Study:

• To investigate the antitumor effects of the natural quassinoid Ailanthone (AIL) in PCa.
• To determine AIL's impact on VM in PCa and elucidate its underlying molecular mechanisms.

Main Methods:

• In vitro studies assessing PCa cell viability, apoptosis, cell-cycle arrest, migration, invasion, stemness, and VM formation.
• Mechanistic investigations involving EGR3, SOCS2, and JAK/STAT3 signaling pathways.
• In vivo xenograft models to evaluate AIL's efficacy and VM inhibition in a tumor microenvironment.

Main Results:

• AIL significantly suppressed PCa cell viability, induced apoptosis and G1/S cell-cycle arrest, and inhibited migration, invasion, stemness, and VM.
• AIL enhanced EGR3 binding to the SOCS2 promoter, leading to SOCS2 upregulation and JAK/STAT3 signaling inhibition.
• In vivo, AIL reduced tumor growth, promoted apoptosis, and attenuated VM, with effects dependent on SOCS2 expression.

Conclusions:

• Ailanthone demonstrates potent anti-tumor and anti-VM activities in prostate cancer.
• The mechanism involves the activation of the EGR3-SOCS2 axis and suppression of JAK/STAT3 signaling.
• AIL holds promise as a therapeutic strategy for advanced and treatment-resistant prostate cancer.