Induction of Chemosensitivity in Human Lung Cancer Cells in Vivo by Adenovirus-mediated Transfer of the Wild-Type p53 Gene

Toshiyoshi Fujiwara, Elizabeth A. Grimm, Tapas Mukhopadhyay, Wei Wei Zhang, Laurie B. Owen-Schaub, Jack A. Roth

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485 Citations (Scopus)

Abstract

Recombinant adenovirus-mediated transfer of the wild-type p53 gene into monolayer cultures or multicellular tumor spheroids of human non small cell lung cancer cell line H358, which has a homozygous deletion of p53, markedly increased the cellular sensitivity of these cells to the chemotherapeutic drug cisplatin. Treated cells underwent apoptosis with specific DNA fragmentation. Direct injection of the p53-adenovirus construct into H358 tumors s.c. implanted into nu/nu mice, followed by i.p. administration of cisplatin, induced massive apoptotic destruction of the tumors. These results support the clinical application of a regimen combining gene replacement using replication-deficient wild-type p53 adenovirus and DNA-damaging drugs for treatment of human cancer.

Original languageEnglish
Pages (from-to)2287-2291
Number of pages5
JournalCancer Research
Volume54
Issue number9
Publication statusPublished - May 1994
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Fujiwara, T., Grimm, E. A., Mukhopadhyay, T., Zhang, W. W., Owen-Schaub, L. B., & Roth, J. A. (1994). Induction of Chemosensitivity in Human Lung Cancer Cells in Vivo by Adenovirus-mediated Transfer of the Wild-Type p53 Gene. Cancer Research, 54(9), 2287-2291.