Additive effects of radiation and docetaxel on murine SCCVII tumors in vivo: special reference to changes in the cell cycle.
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.
Suzuki
Minoru
M
Department of Radiology, Kinki University, School of Medicine, Japan. msuzuki@rri.kyoto-u.ac.jp
Nakamatsu
Kiyoshi
K
Kanamori
Shuichi
S
Masunaga
Shin-Ichiro
S
Nishimura
Yasumasa
Y
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D000077143:Docetaxel; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008938:Mitosis / Q000187:drug effects / Q000528:radiation effects; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000494:pharmacology*; D043823:Taxoids
D019394:Ki-67 Antigen; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel