Influence of cisplatin and doxorubicin on 125I-meta-iodobenzylguanidine uptake in human neuroblastoma cell lines.
The combination of 131I-meta-iodobenzylguanidine (MIBG) with chemotherapy has recently been employed in the treatment of advanced stage neuroblastoma with encouraging results. However, the mechanisms underlying the interaction between these two different modalities of treatment have not yet been explored. In this study, human neuroblastoma cell lines pretreatment with cisplatin and doxorubicin increased cellular 125I-MIBG accumulation in a dose-dependent manner. Cell cycle analysis showed that increased 125I-MIBG accumulation correlated with the drug-induced G2/M phase block. Northern blot analysis demonstrated an increase in gene expression of the noradrenaline transporter induced by doxorubicin, but not by cisplatin treatment. Increased 125I-MIBG accumulation was also observed in murine xenografts of the human neuroblastoma cell line SK-N-DZ or BE(2)M17 treated intraperitoneally (i.p.) with cisplatin or doxorubicin, respectively. These results suggest that the combination of 131I-MIBG and these drugs could selectively increase radiation doses delivered to neuroblastomas.
Meco
D
D
Division of Paediatric Oncology, Catholic University, Rome, Italy.
Lasorella
A
A
Riccardi
A
A
Servidei
T
T
Mastrangelo
R
R
Riccardi
R
R
D019797:3-Iodobenzylguanidine / Q000493:pharmacokinetics*; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015152:Blotting, Northern; D002945:Cisplatin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005434:Flow Cytometry; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009447:Neuroblastoma / Q000188:drug therapy* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000378:metabolism
D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine; D004317:Doxorubicin; D002945:Cisplatin