NK4 gene therapy combined with cisplatin inhibits tumour growth and metastasis of squamous cell carcinoma

Anticancer Res. 2011 Jan;31(1):105-11.

Abstract

Background: NK4 inhibits vascularisation in tumour tissues, thereby arresting tumour growth. However, the antitumour efficacy of individual antiangiogenic molecules expressed in vivo is not sufficiently potent to induce regression in animal models. One of the strategies to overcome this disadvantage is to use chemotherapy.

Materials and methods: This study evaluated the efficacy of combining NK4 gene therapy with cisplatin to treat experimental squamous cell carcinomas. For gene therapy, biodegradable cationised gelatin microspheres were used for the controlled release of NK4 plasmid DNA.

Results: A combined regimen of antiangiogenic gene therapy and low-dose cisplatin led to a marked decrease in tumour volume and vascularity, and caused increased apoptosis compared to NK4 gene therapy alone. Moreover, combination treatment of NK4 gene therapy and low-dose cisplatin dramatically inhibited the formation of lung metastases.

Conclusion: NK4 gene therapy combined with low-dose cisplatin may be an effective regimen for treating oral squamous cell carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Squamous Cell / blood supply
  • Carcinoma, Squamous Cell / secondary*
  • Carcinoma, Squamous Cell / therapy
  • Cisplatin / therapeutic use*
  • Combined Modality Therapy
  • Enzyme-Linked Immunosorbent Assay
  • Genetic Therapy*
  • Hepatocyte Growth Factor / genetics*
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / secondary*
  • Lung Neoplasms / therapy
  • Mice
  • Mice, Inbred C3H
  • Mice, Nude
  • Neovascularization, Pathologic / prevention & control
  • Skin Neoplasms / blood supply
  • Skin Neoplasms / pathology*
  • Skin Neoplasms / therapy
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • HGF protein, human
  • Hepatocyte Growth Factor
  • Cisplatin