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 journalArticle

28 Citations (Scopus)

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 - Dec 1 1997

Fingerprint

p53 Genes
Adenoviridae
Cisplatin
Carcinoma
Neoplasms
Proteins
Genetic Suppression
Human Adenoviruses
bcl-2-Associated X Protein
DNA Fragmentation
Ovarian Neoplasms
Genes
Complementary DNA
Apoptosis
Mutation

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Sensitization of cis-platinum by a recombinant adenovirus vector expressing wild-type p53 gene in human ovarian carcinomas. / Song, Kaimei; Li, Zhuangwu; Seth, Prem; Cowan, Kenneth H; Sinha, Birandra K.

In: Oncology Research, Vol. 9, No. 11-12, 01.12.1997, p. 603-609.

Research output: Contribution to journalArticle

Song, Kaimei ; Li, Zhuangwu ; Seth, Prem ; Cowan, Kenneth H ; Sinha, Birandra K. / Sensitization of cis-platinum by a recombinant adenovirus vector expressing wild-type p53 gene in human ovarian carcinomas. In: Oncology Research. 1997 ; Vol. 9, No. 11-12. pp. 603-609.
@article{e0293e4199814018b1e47ee907bf3b9c,
title = "Sensitization of cis-platinum by a recombinant adenovirus vector expressing wild-type p53 gene in human ovarian carcinomas",
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.",
keywords = "Adenovirus, Drug resistance, Gene therapy, Ovarian carcinoma, cis-Platinum, p53 gene",
author = "Kaimei Song and Zhuangwu Li and Prem Seth and Cowan, {Kenneth H} and Sinha, {Birandra K.}",
year = "1997",
month = "12",
day = "1",
language = "English (US)",
volume = "9",
pages = "603--609",
journal = "Oncology Research",
issn = "0965-0407",
publisher = "Cognizant Communication Corporation",
number = "11-12",

}

TY - JOUR

T1 - Sensitization of cis-platinum by a recombinant adenovirus vector expressing wild-type p53 gene in human ovarian carcinomas

AU - Song, Kaimei

AU - Li, Zhuangwu

AU - Seth, Prem

AU - Cowan, Kenneth H

AU - Sinha, Birandra K.

PY - 1997/12/1

Y1 - 1997/12/1

N2 - 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.

AB - 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.

KW - Adenovirus

KW - Drug resistance

KW - Gene therapy

KW - Ovarian carcinoma

KW - cis-Platinum

KW - p53 gene

UR - http://www.scopus.com/inward/record.url?scp=0031311480&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031311480&partnerID=8YFLogxK

M3 - Article

VL - 9

SP - 603

EP - 609

JO - Oncology Research

JF - Oncology Research

SN - 0965-0407

IS - 11-12

ER -