Sensitization of cis-platinum by a recombinant adenovirus vector expressing wild-type p53 gene in human ovarian carcinomas

Kaimei Song, Zhuangwu Li, Prem Seth, Kenneth H. Cowan, Birandra K. Sinha

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Mutations of the tumor suppressor wild-type p53 gene have been implicated in the development of resistance to anticancer drugs. We have examined the role of wild-type p53 in resistance to cis-diamminedichloroplatinum (II) (CDDP) in human ovarian cancer cells using a recombinant adenovirus containing human wild-type p53 cDNA (Adwtp53). In this study we used the human ovarian A2780 tumor cells (wtp53), which are sensitive to CDDP and A2780/CP tumor cells (nonfunctional/mutant p53) and are resistant to CDDP. Studies show that introduction of wtp53 protein via adenovirus gene transfer into A2780/CP cells significantly sensitized these cells to CDDP cytotoxicity, indicating wtp53 was involved in resistance to CDDP. We found that introduction of wtp53 protein also resulted in growth arrest of A2780/CP tumor cells whereas the parent A2780 cells were significantly less sensitive to Adwtp53. This synthesis of wtp53 protein induced by Adwtp53 in A2780/CP cells resulted in a significant increase in the expression of Bax protein without significantly effecting the expression of bcl2 protein, and induced a dose-dependent increase in the nucleosomal DNA fragmentation. The presence of CDDP further enhanced this apoptosis, causing a 30-fold sensitization of A2780/CP cells to CDDP. These results indicate that mutation of p53 protein in A2780/CP ovarian tumor cells resulted in the resistance to CDDP and that combinations of wtp53 gene and CDDP may result in sensitization of mutant p53-containing tumors to chemogenetherapy.

Original languageEnglish (US)
Pages (from-to)603-609
Number of pages7
JournalOncology Research
Volume9
Issue number11-12
StatePublished - 1997
Externally publishedYes

Keywords

  • Adenovirus
  • Drug resistance
  • Gene therapy
  • Ovarian carcinoma
  • cis-Platinum
  • p53 gene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Sensitization of cis-platinum by a recombinant adenovirus vector expressing wild-type p53 gene in human ovarian carcinomas'. Together they form a unique fingerprint.

Cite this