Reversal of CPT-11 resistance of lung cancer cells by adenovirus-mediated gene transfer of the human carboxylesterase cDNA. Academic Article Article uri icon

Overview

MeSH

  • Adenocarcinoma
  • Adenoviruses, Human
  • Carboxylesterase
  • Cell Division
  • Cell Survival
  • Clone Cells
  • DNA Topoisomerases, Type I
  • DNA, Complementary
  • Drug Resistance, Neoplasm
  • Genetic Vectors
  • Humans
  • Lung Neoplasms
  • Recombinant Proteins
  • Transfection
  • Tumor Cells, Cultured

MeSH Major

  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Camptothecin
  • Carboxylic Ester Hydrolases

abstract

  • To evaluate the concept that transfer of the human carboxylesterase (CE) gene will overcome the drug resistance of a solid tumor to CPT-11 (irinotecan), we used an adenovirus vector (AdCMV.CE) carrying human CE cDNA to infect CPT-11-resistant A549 human adenocarcinoma cells (A549/CPT) in vitro and in vivo and evaluated cell growth over time. The A549/CPT cells, selected by stepwise and continuous exposure of parental A549 cells to CPT-11 over 10 months, had a 6-fold resistance to CPT-11 and 42% CE activity in comparison with parental A549 cells. AdCMV.CE infection resulted in an increase in functional CE protein in resistant cells in vitro that was sufficient to convert CPT-11 to its active metabolite, SN-38, and effectively suppressed resistant cell growth in vitro in the presence of CPT-11. When AdCMV.CE was directly injected into established s.c. resistant A549-based tumors in nude mice receiving CPT-11, there was a 1.8-fold reduction in tumor size at day 20 compared to that of controls (P < 0.05). These observations suggest that adenovirus-mediated gene transfer of the human CE gene and concomitant administration of CPT-11 may have potential as a strategy for local control of acquired CPT-11 resistance of solid tumors.

publication date

  • October 1, 1998

has subject area

  • Adenocarcinoma
  • Adenoviruses, Human
  • Antineoplastic Agents
  • Antineoplastic Agents, Phytogenic
  • Camptothecin
  • Carboxylesterase
  • Carboxylic Ester Hydrolases
  • Cell Division
  • Cell Survival
  • Clone Cells
  • DNA Topoisomerases, Type I
  • DNA, Complementary
  • Drug Resistance, Neoplasm
  • Genetic Vectors
  • Humans
  • Lung Neoplasms
  • Recombinant Proteins
  • Transfection
  • Tumor Cells, Cultured

Research

keywords

  • Comparative Study
  • Journal Article

Identity

Language

  • eng

PubMed ID

  • 9766666

Additional Document Info

start page

  • 4368

end page

  • 4374

volume

  • 58

number

  • 19