Growth suppression of human laryngeal squamous cell carcinoma by adenovirus-mediated tissue factor pathway inhibitor gene 2

Laryngoscope. 2006 Apr;116(4):596-601. doi: 10.1097/01.mlg.0000205589.84020.d2.

Abstract

Objective: The purpose of this study was to explore the inhibiting role of adenoviral-mediated (Ad)-tissue factor pathway inhibitor (TFPI)-2 gene in the growth of laryngeal squamous cell carcinoma (LSCC).

Study design: The nude mice bearing LSCC were prepared by intracutaneous injection of Hep-2 cell. Gene therapy was performed by injecting adenoviruses carrying TFPI-2 gene around tumors in the animal model.

Methods: Eighteen nude mice bearing Hep-2 cell tumor were randomly separated into the treated group and control group. The former were injected with recombinant adenovirus Ad-TFPI-2 around the tumor, and the later were injected with equivalent Ad-LacZ. After treatment, differences of tumor weight, volume, and ultrastructure of tumor cells between these two groups were observed by measuring and using transmission electron microscope. Apoptosis in Hep-2 xenotransplants was detected using the terminal deoxy-transferase-mediated dUTP nick end labeling. In addition, the expressions of TFPI-2 protein and proliferating cell nuclear antigen (PCNA) in tumor tissues were detected using Western blot and immunohistochemistry, respectively.

Results: The average weight and volume of tumor in the treated group were significantly lower than that in the control group (P < .01). The PCNA index was obviously lower in the tumors treated group than that in the control group (P < .01). In addition, cell apoptosis was observed in xenotransplants of the treated group but not in the control group.

Conclusion: Peritumor injection of Ad-TFPI-2 can inhibit growth of LSCC in nude mice model, and TFPI-2 might be a desirable gene for gene therapy in LSCC.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Apoptosis
  • Blotting, Western
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology*
  • Carcinoma, Squamous Cell / therapy
  • Cell Line, Tumor
  • Factor VIIa / antagonists & inhibitors
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Glycoproteins / biosynthesis
  • Glycoproteins / genetics
  • Glycoproteins / therapeutic use*
  • Humans
  • Immunohistochemistry
  • Laryngeal Neoplasms / metabolism
  • Laryngeal Neoplasms / pathology*
  • Laryngeal Neoplasms / therapy
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Electron, Transmission
  • Proliferating Cell Nuclear Antigen / metabolism
  • Serine Proteinase Inhibitors / genetics
  • Serine Proteinase Inhibitors / therapeutic use*

Substances

  • Glycoproteins
  • Proliferating Cell Nuclear Antigen
  • Serine Proteinase Inhibitors
  • tissue-factor-pathway inhibitor 2
  • Factor VIIa