P53-independent response to cisplatin and oxaliplatin in mmtv-ras mouse salivary tumors

Thierry Petit, David J. Bearss, Dean A. Troyer, Ruben M. Munoz, Jolene J. Windle

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

A transgenic mouse tumor model was used to investigate the role of p53 in tumor response to two different platinum-based chemotherapeutic agents: (a) cisplatin and (b) oxaliplatin, a diaminocyclohexane platine recently introduced into the clinic. MMTV-v-Ha-ras transgenic mice were interbred to p53-deficient mice to generate mice that develop salivary tumors either possessing or lacking p53. Tumor-bearing mice were then treated on either a 9-day schedule to assess overall tumor growth response or on a short-term treatment schedule to assess effects on cell cycle parameters and apoptosis. Both agents induced significant apoptosis and promoted overall tumor regression, regardless of the p53 status of the tumor. This is in contrast to previous studies using this model in which treatment with paclitaxel or doxorubicin promoted tumor growth arrest but not apoptosis. These findings indicate that even in the context of an activated ras gene that potentially mediates suppression of apoptosis, both cisplatin and oxaliplatin are capable of promoting an efficient p53-independent tumor response.

Original languageEnglish (US)
Pages (from-to)165-171
Number of pages7
JournalMolecular cancer therapeutics
Volume2
Issue number2
StatePublished - Feb 2003

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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