Additive effects of radiation and docetaxel on murine SCCVII tumors in vivo: special reference to changes in the cell cycle

Radiat Res. 2003 Jun;159(6):799-804. doi: 10.1667/0033-7587(2003)159[0799:aeorad]2.0.co;2.

Abstract

The purpose of the present study was to investigate the effects of a combination of docetaxel and irradiation in vivo with special reference to docetaxel-arrested G(2)/M-phase cells. At 24 and 48 h after intraperitoneal administration of docetaxel (90 mg/kg), tumor-bearing mice were irradiated with (60)Co gamma rays. Cell cycle distribution was analyzed by a DNA-Ki-67 double staining method using flow cytometry. An accumulation of cells in the G(2)/M phase of up to approximately 40% was observed 24 h after administration of docetaxel. Between 24 and 72 h, the percentage of cells arrested in G(2)/M phase that expressed Ki-67 decreased from 37.2% to 13.8%, in accordance with the increase in the Ki-67-negative G(2)/M-phase fraction. More than half of the cells arrested in G(2)/M phase lost their expression of Ki-67 protein between 24 and 72 h. The G(1)-phase fraction decreased from 28.4% to 8.6% at 24 h after docetaxel treatment; this remained unchanged at 72 h. These flow cytometry data suggested that docetaxel-arrested G(2)/M-phase cells did not enter the next cell cycle and were killed by docetaxel alone. Our data showed that arrest of cells in G(2)/M phase does not contribute to the synergism that has been reported for combinations of docetaxel and radiation in in vivo tumor models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy*
  • Combined Modality Therapy
  • Docetaxel
  • Ki-67 Antigen / analysis
  • Male
  • Mice
  • Mice, Inbred C3H
  • Mitosis / drug effects
  • Mitosis / radiation effects
  • Paclitaxel / analogs & derivatives*
  • Paclitaxel / pharmacology*
  • Taxoids*

Substances

  • Ki-67 Antigen
  • Taxoids
  • Docetaxel
  • Paclitaxel