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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
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PI3K δ inhibitor PI-3065 induces apoptosis in hepatocellular carcinoma cells by targeting survivin

Yuze Wei1, Weiwei Ke2, Zaiming Lu1

  • 1Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, 110004, China.

Chemico-Biological Interactions
|January 9, 2023
PubMed

Insights

PI-3065, a novel drug, effectively inhibits hepatocellular carcinoma (HCC) cell growth and triggers apoptosis by targeting survivin. This promising agent shows potential for treating HCC with minimal toxicity to normal liver cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Hepatocellular carcinoma (HCC) presents a significant global health challenge with limited treatment options.
  • Phosphoinositide 3-kinase (PI3K) signaling is frequently dysregulated in HCC, making it a potential therapeutic target.
  • The efficacy and mechanisms of PI-3065, a PI3Kδ inhibitor, against HCC are not well understood.

Purpose of the Study:

  • To investigate the antitumor effects of PI-3065 on hepatocellular carcinoma (HCC) cells.
  • To elucidate the underlying molecular mechanisms of PI-3065's action in HCC.
  • To evaluate the in vivo efficacy of PI-3065 in a preclinical HCC model.

Main Methods:

  • In vitro studies using HCC cell lines to assess cell viability, apoptosis, mitochondrial potential, and cytochrome C release.
  • In vitro assays for colony formation, migration, and epithelial-mesenchymal transition (EMT).
  • In vivo studies using nude mouse xenograft models to evaluate tumor growth inhibition.

Main Results:

  • PI-3065 demonstrated dose- and time-dependent inhibition of HCC cell viability and induced apoptosis.
  • PI-3065 selectively induced apoptosis in HCC cells without significant toxicity to normal liver cells.
  • Mechanistically, PI-3065 inhibited survivin expression, disrupted mitochondrial membrane potential, and promoted cytochrome C release, suppressing HCC cell proliferation, migration, and EMT.
  • PI-3065 significantly inhibited HCC tumor growth in vivo by targeting survivin.

Conclusions:

  • PI-3065 exhibits potent anti-HCC activity both in vitro and in vivo.
  • The drug functions by specifically inhibiting survivin expression, leading to apoptosis and reduced tumor progression.
  • PI-3065 represents a potential novel therapeutic agent for hepatocellular carcinoma treatment.
Keywords:
ApoptosisHepatocellular carcinomaPI-3065PI3K inhibitorSurvivin

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