Cisplatin enhances the p53-independent apoptosis induced by a topoisomerase I inhibitor (CPT-11) in the lens epithelial tumors in transgenic mice.
We reported that CPT-11 could induce apoptosis in mouse lens epithelial tumors when it was administered to pregnant alphaT3 mice which developed epithelial cell carcinoma in situ in the lens in the perinatal period. p53-deficient alphaT3 mice were generated to analyze the influence of p53 status on tumor cells under combined chemotherapy. On the 16-18th gestational day, alphaT3 received a single i.p. administration of both CPT-11 and Cisplatin, and fetal lens epithelial tumors were examined two days later. Apoptosis in the p53-wild-type alphaT3 tumors was observed in a Cisplatin dose-dependent manner. In addition, it was found that Cisplatin augmented CPT-11-induced p53-independent apoptosis in p53-deficient alphaT3 mice.
Nakamura
Takafumi
T
Department of Obstetrics and Gynecology, Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan. tn@ms.toyama-mpu.ac.jp
Nakajima
Yasuo
Y
Enomoto
Takayuki
T
Hori
Shinichi
S
Hidaka
Takao
T
Murata
Yuji
Y
Saito
Shigeru
S
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols; D017209:Apoptosis; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004848:Epithelium / Q000378:metabolism*; D005838:Genotype; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D000077146:Irinotecan; D007908:Lens, Crystalline / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D016133:Polymerase Chain Reaction; D015398:Signal Transduction; D059004:Topoisomerase I Inhibitors; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D016159:Tumor Suppressor Protein p53; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin