Suppression of tumor growth in xenograft model mice by programmed cell death 4 gene delivery using folate-PEG-baculovirus

Cancer Gene Ther. 2010 Nov;17(11):751-60. doi: 10.1038/cgt.2010.28. Epub 2010 Jun 11.

Abstract

Cancer gene therapy using tumor suppressor genes is considered to be an attractive approach for arresting cell growth and inducing apoptosis. Programmed cell death 4 (Pdcd4) is a tumor suppressor gene, which prevents tumorigenesis and tumor progression. To address the issue of whether expression of PDCD4 protein induces apoptosis in cancerous cells, the Pdcd4 gene was delivered using folate-PEG-baculovirus. Folate-PEG-baculovirus containing Pdcd4 gene (F-P-Bac-Pdcd4) was constructed by attachment of F-PEG to the baculovirus surface using chemical modification. The F-P-Bac-Pdcd4 showed enhanced transduction efficiency, efficiently expressed PDCD4 protein, and induced apoptosis in human epidermal carcinoma (KB) cells as compared with an unmodified baculovirus. In a tumor xenograft study, injection of F-P-Bac-Pdcd4 into tumors established from the KB cell line by subcutaneous implantation significantly suppressed tumor growth and induced apoptosis. Thus, this study shows a new baculovirus-mediated tumor suppressor gene delivery system for cancer therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / metabolism*
  • Baculoviridae / genetics*
  • Baculoviridae / metabolism
  • Carcinoma / genetics
  • Carcinoma / pathology
  • Carcinoma / therapy*
  • Cell Line, Tumor
  • Folic Acid / analogs & derivatives
  • Folic Acid / metabolism
  • Gene Expression Regulation, Neoplastic
  • Genes, Tumor Suppressor*
  • Genetic Therapy
  • Humans
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Polyethylene Glycols
  • RNA-Binding Proteins / metabolism*
  • Transduction, Genetic*
  • Xenograft Model Antitumor Assays

Substances

  • Apoptosis Regulatory Proteins
  • Pdcd4 protein, mouse
  • RNA-Binding Proteins
  • poly(ethylene glycol)-folate
  • Polyethylene Glycols
  • Folic Acid