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PACE4 regulates apoptosis in human prostate cancer cells via endoplasmic reticulum stress and mitochondrial signaling

Zhiyong Yao1, Bin Sun1, Quan Hong1

  • 1Department of Urology, Air Force General Hospital of People's Liberation Army, Beijing, People's Republic of China.

Drug Design, Development and Therapy
|November 26, 2015
PubMed
Abstract

Insights

PACE4 small interfering (si)RNA demonstrated antitumor effects in prostate cancer by inducing apoptosis. This suggests PACE4 may be a therapeutic target, acting via mitochondrial and endoplasmic reticulum stress pathways.

Area of Science:

  • Oncology
  • Molecular Biology

Background:

  • Proprotein convertase PACE4 processes substrates crucial for tumor progression.
  • The role of PACE4 in prostate cancer cell apoptosis remains unelucidated.

Purpose of the Study:

  • To investigate the role of PACE4 in prostate cancer cell apoptosis.
  • To explore the therapeutic potential of targeting PACE4 in prostate cancer.

Main Methods:

  • Human prostate cancer cell lines (DU145, LNCaP, PC3) were transfected with PACE4 small interfering (si)RNA.
  • Apoptosis was assessed using Cell Counting Kit-8 (CCK-8), MTT assay, cell cycle analysis, Hoechst staining, caspase-3/7 activity, and western blot analysis.

Main Results:

  • PACE4 siRNA induced apoptosis and exhibited antitumor activity in prostate cancer cells.
  • PACE4 knockdown increased the Bax/Bcl-2 ratio, leading to cytochrome c release and activating mitochondrial apoptosis.
  • Endoplasmic reticulum stress was induced, evidenced by increased GRP78, GRP94, p-PERK, and p-eIF2α expression.

Conclusions:

  • PACE4 siRNA exerts antitumor effects through mitochondrial and endoplasmic reticulum stress pathways.
  • Targeting PACE4 represents a potential novel therapeutic strategy for prostate cancer.
Keywords:
Bax/Bcl-2GRP78gene knockdownsmall interfering RNAtumor growth

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