Effect of paclitaxel pretreatment on radiation-induced p53-dependent apoptosis.
The aim of this study was to investigate the effect of paclitaxel on radiation-induced p53-dependent apoptosis. A human ependymoblastoma transplanted to nude mice was used. They were treated with paclitaxel (40 mg/kg), irradiation (2 Gy), or a combination of both. Apoptosis was markedly increased in the irradiation group. p53 protein expression was well correlated with the frequency of radiation-induced apoptosis. There was only a slight increase in apoptosis in the paclitaxel group, with little p53 protein expression. In the combination group, the frequency of apoptosis varied with the time intervals, and the group irradiated 12 h after paclitaxel administration showed much less apoptosis than the irradiation group. The Ki-67 labeling index in the paclitaxel group was always higher than before administration. The present study indicates that p53-dependent apoptosis was frequently induced in the human tumor in vivo by irradiation, but not by paclitaxel alone. When combined with irradiation, the timing affected the frequency of apoptosis and the degree of p53 protein expression.
Kawashima
M
M
Department of Radiology and Radiation Oncology, Gunma University School of Medicine, Japan.
Hasegawa
M
M
Hayakawa
K
K
Nasu
S
S
Toda
H
H
Suzuki
Y
Y
Mitsuhashi
N
N
Niibe
H
H
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000528:radiation effects*; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D000972:Antineoplastic Agents, Phytogenic; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; D017239:Paclitaxel