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Published on: July 21, 2018

MAPK and PI3K inhibition reduces proliferation of Barrett's adenocarcinoma in vitro

Linda Vona-Davis1, Krista Frankenberry, Cynthia Cunningham

  • 1Department of Surgery, West Virginia University, Morgantown, West Virginia 26506-9238, USA.

The Journal of Surgical Research
|June 21, 2005
PubMed
Abstract

Insights

Inhibiting mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways significantly reduced Barrett's adenocarcinoma cell proliferation in vitro. Pro-apoptotic effects were observed in wild-type p53 cells, suggesting therapeutic potential.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Esophageal adenocarcinoma frequently develops from Barrett's esophagus.
  • Mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways are crucial for cell survival.
  • This study investigated the effects of inhibiting these pathways in Barrett's adenocarcinoma.

Purpose of the Study:

  • To evaluate the antiproliferative and pro-apoptotic effects of MAPK and PI3K inhibition in Barrett's adenocarcinoma cell lines.
  • To determine if p53 status influences the response to pathway inhibition.

Main Methods:

  • Two Barrett's-associated adenocarcinoma cell lines (SEG-1 with wild-type p53 and BIC-1 with mutant p53) were treated with MAPK (U0126) and PI3K (LY294002) inhibitors.
  • Cell viability was assessed using MTT assays, and apoptosis/necrosis were measured by Annexin V-FITC assay.
  • Statistical significance was determined using ANOVA.

Main Results:

  • Both inhibitors significantly reduced cell proliferation in SEG-1 cells (wild-type p53) and BIC-1 cells (mutant p53) at 72 hours.
  • Apoptotic activity significantly increased in SEG-1 cells, while necrosis decreased.
  • No significant changes in apoptosis or necrosis were observed in BIC-1 cells.

Conclusions:

  • MAPK and PI3K inhibition demonstrate significant antiproliferative effects against Barrett's adenocarcinoma in vitro.
  • Pro-apoptotic mechanisms are prominent in wild-type p53 Barrett's adenocarcinoma cells.
  • Further research is needed to explore clinical applications for treating this disease.

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