Aerosol delivery of urocanic acid-modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice

Hua Jin, Hee Kim Tae, Soon Kyung Hwang, Seung Hee Chang, Woo Kim Hyun, Hanjo K. Anderson, Han Woong Lee, Kee Ho Lee, Nancy H. Colburn, Hsin Sheng Yang, Myung Haing Cho, Su Cho Chong

Research output: Contribution to journalArticle

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Abstract

The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for development of novel treatment options. Although several genes have been investigated for their antitumor activities through gene delivery, problems surrounding the methods used, such as efficiency, specificity, and toxicity, hinder application of such therapies in clinical settings. Aerosol gene delivery as nonviral and noninvasive method for gene therapy may provide an alternative for a safer and more effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid - modified chitosan (UAC) designed in previous study was used as a gene carrier. The efficiency of UAC carrier in lungs was confirmed, and the potential effects of the programmed cell death protein 4 (PDCD4) tumor suppressor gene on three major pathways (apoptosis, cell cycle, and angiogenesis) were evaluated. Aerosol containing UAC/PDCD4 complexes was delivered into K-ras null lung cancer model mice through the nose-only inhalation system developed by our group. Delivered UAC/PDCD4 complex facilitated apoptosis, inhibited pathways important for cell proliferation, and efficiently suppressed pathways important for tumor angiogenesis. In summary, results obtained by Western blot analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase - mediated nick end labeling assay suggest that our aerosol gene delivery technique is compatible with in vivo gene delivery and can be applied as a noninvasive gene therapy.

Original languageEnglish
Pages (from-to)1041-1049
Number of pages9
JournalMolecular Cancer Therapeutics
Volume5
Issue number4
DOIs
Publication statusPublished - 2006 Apr 1

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Urocanic Acid
Chitosan
Aerosols
Cell Cycle
Cell Death
Apoptosis
Lung
Apoptosis Regulatory Proteins
Genes
Lung Neoplasms
Genetic Therapy
DNA Nucleotidylexotransferase
Therapeutics
Tumor Suppressor Genes
Nose
Inhalation
Western Blotting
Immunohistochemistry
Cell Proliferation
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Jin, Hua ; Tae, Hee Kim ; Hwang, Soon Kyung ; Chang, Seung Hee ; Hyun, Woo Kim ; Anderson, Hanjo K. ; Lee, Han Woong ; Lee, Kee Ho ; Colburn, Nancy H. ; Yang, Hsin Sheng ; Cho, Myung Haing ; Chong, Su Cho. / Aerosol delivery of urocanic acid-modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice. In: Molecular Cancer Therapeutics. 2006 ; Vol. 5, No. 4. pp. 1041-1049.
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Aerosol delivery of urocanic acid-modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice. / Jin, Hua; Tae, Hee Kim; Hwang, Soon Kyung; Chang, Seung Hee; Hyun, Woo Kim; Anderson, Hanjo K.; Lee, Han Woong; Lee, Kee Ho; Colburn, Nancy H.; Yang, Hsin Sheng; Cho, Myung Haing; Chong, Su Cho.

In: Molecular Cancer Therapeutics, Vol. 5, No. 4, 01.04.2006, p. 1041-1049.

Research output: Contribution to journalArticle

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AU - Jin, Hua

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