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Inducible nuclear factor-kappaB activation contributes to chemotherapy resistance in gastric cancer

E Ramsay Camp1, Jing Li, Douglas J Minnich

  • 1Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610, USA.

Journal of the American College of Surgeons
|July 28, 2004
PubMed
Abstract

Insights

Inhibiting nuclear factor-kappaB (NF-kappaB) with Ad.IkappaBalpha-SR enhances chemotherapy effectiveness against gastric cancer. This approach boosts the antitumor impact of 5-fluorouracil and irinotecan, showing promise for new cancer treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Nuclear factor-kappaB (NF-kappaB) activation can confer chemoresistance in cancer cells.
  • Targeting NF-kappaB may overcome resistance to chemotherapy in gastric cancer.

Purpose of the Study:

  • To investigate if inhibiting NF-kappaB with Ad.IkappaBalpha-SR can enhance the efficacy of 5-fluorouracil (5-FU) and irinotecan in gastric cancer cells.
  • To evaluate the potential of Ad.IkappaBalpha-SR as a novel antineoplastic strategy.

Main Methods:

  • Gastric cancer cell lines (NCI-N87 and AGS) were treated with Ad.IkappaBalpha-SR followed by 5-FU or SN-38 (irinotecan metabolite).
  • NF-kappaB activation was measured using luciferase reporter and electrophoretic mobility shift assays.
  • Cell growth inhibition was assessed via proliferation assays, and apoptosis was quantified using flow cytometry and caspase 3/7 assays.

Main Results:

  • 5-FU and SN-38 significantly induced NF-kappaB activation.
  • Ad.IkappaBalpha-SR effectively inhibited NF-kappaB activation.
  • Pretreatment with Ad.IkappaBalpha-SR significantly enhanced growth inhibition and apoptosis induction by 5-FU and SN-38 in both cell lines.

Conclusions:

  • NF-kappaB activation in gastric cancer contributes to chemoresistance.
  • Inhibition of NF-kappaB using Ad.IkappaBalpha-SR potentiates the antitumor effects of chemotherapy.
  • Ad.IkappaBalpha-SR represents a promising novel strategy for gastric cancer treatment.

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