Suzuki, M., Nakamatsu, K., Kanamori, S., Masunaga, S. and Nishimura, Y. Additive Effects of Radiation and Docetaxel on Murine SCCVII Tumors In Vivo: Special Reference to Changes in the Cell Cycle. Radiat. Res. 159, 799–804 (2003).
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 G2/M-phase cells. At 24 and 48 h after intraperitoneal administration of docetaxel (90 mg/kg), tumor-bearing mice were irradiated with 60Co γ rays. Cell cycle distribution was analyzed by a DNA-Ki-67 double staining method using flow cytometry. An accumulation of cells in the G2/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 G2/M phase that expressed Ki-67 decreased from 37.2% to 13.8%, in accordance with the increase in the Ki-67-negative G2/M-phase fraction. More than half of the cells arrested in G2/M phase lost their expression of Ki-67 protein between 24 and 72 h. The G1-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 G2/M-phase cells did not enter the next cell cycle and were killed by docetaxel alone. Our data showed that arrest of cells in G2/M phase does not contribute to the synergism that has been reported for combinations of docetaxel and radiation in in vivo tumor models.