Induction of p53-dependent apoptosis in vivo by nedaplatin and ionizing radiation.
p53 protein expression, apoptosis and growth delay induced by nedaplatin, a novel platinum compound, were investigated in vivo, and compared with those induced by ionizing radiation. A human ependymoblastoma with wild-type p53 was transplanted subcutaneously to the thighs of nude mice. The incidences of p53 protein-positive cells and apoptosis in tumors increased following exposure to ionizing radiation. In tumors treated with nedaplatin, they also increased, but the incidences of p53 protein-positive cells and apoptosis induced by 32 mg/kg nedaplatin, 1/2 LD50, were lower than those induced by 1 Gy irradiation. However, growth-delay assay showed no significant difference between the efficacy of 32 mg/kg nedaplatin and that of 1 Gy irradiation. These results suggest that the main antineoplastic activity caused by nedaplatin may be mediated through different mechanisms than those of the p53-dependent early apoptosis.
Nakamura
Y
Y
Department of Radiology and Radiation Oncology, Gunma University School of Medicine, Maebashi, Gunma 371-8511, Japan.
Hasegawa
M
M
Hayakawa
K
K
Matsuura
M
M
Suzuki
Y
Y
Nasu
S
S
Yamakawa
M
M
Mitsuhashi
N
N
Niibe
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D003131:Combined Modality Therapy; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D018242:Neuroectodermal Tumors, Primitive / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000532:radiotherapy; D009944:Organoplatinum Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D016159:Tumor Suppressor Protein p53; C053989:nedaplatin