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Updated: May 17, 2026

Therapeutic Gene Delivery and Transfection in Human Pancreatic Cancer Cells using Epidermal Growth Factor Receptor-targeted Gelatin Nanoparticles
08:35

Therapeutic Gene Delivery and Transfection in Human Pancreatic Cancer Cells using Epidermal Growth Factor Receptor-targeted Gelatin Nanoparticles

Published on: January 4, 2012

Gene therapy of pancreatic cancer targeting the K-Ras oncogene

V Lisiansky1, I Naumov, S Shapira

  • 1The Integrated Cancer Prevention Center, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.

Cancer Gene Therapy
|October 27, 2012
PubMed

Insights

This study developed a novel gene therapy to target Ras-mutated pancreatic cancer cells by overexpressing PUMA. The treatment selectively killed cancer cells while sparing normal cells, showing promise for future cancer therapies.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gene Therapy

Background:

  • Ras mutations are prevalent in pancreatic cancer, driving uncontrolled cell growth and resistance to apoptosis.
  • Targeting Ras-transformed cells selectively is crucial for effective pancreatic cancer treatment.

Purpose of the Study:

  • To investigate the selective killing of Ras-mutated cancer cells by overexpressing the pro-apoptotic protein PUMA using a Ras-responsive promoter.
  • To evaluate the efficacy and safety of this gene therapy approach in preclinical models.

Main Methods:

  • Construction of adenoviral vectors (Ad-PY4/PY5-PUMA) with PUMA under a Ras-responsive promoter.
  • Testing in pancreatic cancer cell lines (Colo357, Panc1, MiaPaca) and normal enterocytes (IEC18) with and without K-Ras transformation.
  • Assessment of cell viability (MTT assay) and apoptosis (FACS).
  • In vivo evaluation of tumor growth inhibition in athymic nude mice.

Main Results:

  • Ad-PY4/PY5-PUMA significantly inhibited growth (40-50%) and induced apoptosis in Ras-highly active cells, sparing normal cells.
  • The control vector (Ad-SV40-PUMA) did not induce cell death.
  • Selective and high PUMA expression was observed in infected cancer cells.
  • In vivo, Ad-PY4-PUMA inhibited tumor growth by approximately 35% compared to the control.

Conclusions:

  • Selective PUMA overexpression effectively inhibits Ras-transformed cell growth while preserving normal cells.
  • This gene therapy strategy demonstrates potential as a safe and effective approach for targeting Ras-mutated tumors.

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