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Updated: Feb 15, 2026

An Orthotopic Murine Model of Human Prostate Cancer Metastasis
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Published on: September 18, 2013

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p62 as a therapeutic target for inhibition of autophagy in prostate cancer

Lei Wang1, Donghern Kim2, James T F Wise3

  • 1Center for Research on Environmental Disease, University of Kentucky, Lexington, Kentucky.

The Prostate
|January 26, 2018
PubMed
Abstract

Insights

The drug Verteporfin inhibits prostate cancer growth by targeting the p62 protein to block autophagy. This FDA-approved drug shows promise for treating advanced prostate cancer by inhibiting p62 and its downstream effects.

Area of Science:

  • Oncology
  • Cell Biology
  • Drug Discovery

Background:

  • Prostate cancer remains a significant health challenge, necessitating novel therapeutic strategies.
  • Autophagy, a cellular degradation process, is implicated in cancer progression and presents a potential therapeutic target.
  • p62 is a key protein in autophagy regulation and has emerged as a potential target for therapeutic intervention.

Purpose of the Study:

  • To investigate the therapeutic potential of targeting p62 for autophagy inhibition in advanced prostate cancer.
  • To evaluate Verteporfin, an FDA-approved drug targeting p62, as a potential treatment for prostate cancer.

Main Methods:

  • Forced expression of p62 in prostate cancer (PC-3) and normal prostate epithelial cells (RWPE-1, PZ-HPV7) using plasmids.
  • Assessment of autophagosomes and autophagic flux via mCherry-GFP-LC3 tandem fluorescence protein construct transfection.
  • Measurement of apoptosis using Annexin V/PI staining and tumorigenesis via a xenograft tumor growth model.

Main Results:

  • Verteporfin inhibited PC-3 cell growth and colony formation by generating crosslinked p62 oligomers, thus inhibiting autophagy.
  • Verteporfin treatment led to constitutive activation of Nrf2 and its target genes (Bcl-2, TNF-α), and inhibited starvation-induced autophagic flux.
  • In normal prostate cells, forced p62 expression conferred apoptosis resistance; Verteporfin inhibited tumorigenesis in both normal and cancer cells.

Conclusions:

  • p62 demonstrates significant potential as a therapeutic target for prostate cancer treatment.
  • Verteporfin exhibits therapeutic promise against prostate cancer by inhibiting autophagy through a novel p62-targeting mechanism.
Keywords:
Nrf2autophagyp62prostate cancerverteporfin

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