Therapeutic effect of a retroviral wild-type p53 expression vector in an orthotopic lung cancer model

J Natl Cancer Inst. 1994 Oct 5;86(19):1458-62. doi: 10.1093/jnci/86.19.1458.


Background: Mutations in the p53 tumor suppressor gene (also known as TP53) are common in human lung cancers. The wild-type form of p53 is dominant over the mutant; thus, restoration of wild-type p53 function in lung cancer cells may suppress their growth as tumors.

Purpose: We investigated the therapeutic efficacy of direct administration of a retroviral wild-type p53 (wt-p53) expression vector (LNp53B) in an orthotopic human lung cancer model in nu/nu mice.

Methods: Proliferation of H226Br cells was determined by cell counting after infection with LNp53B in vitro. Irradiated (350 cGy) female BALB/c nu/nu mice were inoculated intratracheally with 2 x 10(6) H226Br cells (whose p53 gene has a homozygous mutation at codon 254) and treated beginning 3 days later with an intratracheal instillation of LNp53B retroviral supernatant for 3 days.

Results: Infection with LNp53B inhibited proliferation of H226Br cells in vitro. Thirty days after tumor cell inoculation, 62%-80% of the control mice showed macroscopic tumors of the right main stem bronchus. LNp53B suppressed H226Br tumor formation in 62%-100% of mice, and the effect was abrogated by dilution of the retroviral supernatant with inactive vector.

Conclusions: Direct administration of a retroviral vector expressing wt-p53 may inhibit local growth in vivo of human lung cancer cells with abnormal p53 expression.

Implications: Development of gene-replacement treatment strategies based on the type of mutations found in target cancers is warranted and may lead to the development of new adjunctive therapies and gene-specific prevention strategies for lung cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Blotting, Southern
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Female
  • Genes, p53*
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / therapy*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Sequence Data
  • Neoplasm Transplantation
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • RNA, Neoplasm / analysis
  • Retroviridae*
  • Tumor Cells, Cultured


  • RNA, Messenger
  • RNA, Neoplasm