Chemotherapeutic enhancement of antitumor effect of Auger electrons-emitting antisense oligonucleotides on human neuroblastoma

俄歇电子能够在mRNA（信使核糖核酸）中产生断裂，使它们有可能用于治疗恶性肿瘤。研究in -111标记的N-myc反义寡核苷酸与顺式二胺二氯铂（CDDP）联合应用对人神经母细胞瘤腹腔移植BALB/c胸腺小鼠的抗肿瘤作用。在其他地方也发现了in -111标记的N-myc反义寡核苷酸对人神经母细胞瘤细胞和移植到胸腺裸鼠的作用。肿瘤对CDDP的反应与给药剂量有关。当CDDP剂量为5 mg/kg/次时，观察到肿瘤消退。CDDP剂量约为2 mg/kg/注射组肿瘤生长迟缓。当用in -111标记的N-myc反义寡核苷酸给药CDDP时，用in -111标记的N-myc反义寡核苷酸组观察到肿瘤消退，用in -111标记的N-myc反义寡核苷酸低剂量组观察到肿瘤生长迟缓。这些结果表明，CDDP增强了in -111标记的N-myc反义寡核苷酸对BALB/c胸腺小鼠移植神经母细胞瘤的抗肿瘤作用。

Auger electrons are able to create breaks in mRNA (messenger ribonucleic acids), giving them possible therapeutic utility against malignant tumor. The antitumor effect of combined use of In-111-labeled N-myc antisense oligonucleotides and cis-diamminedichloroplatinum (II) (CDDP) was investigated in human neuroblastoma intraperitoneally transplanted to BALB/c athymic mice. The effects of In-111-labeled N-myc antisense oligonucleotides against human neuroblastoma cells and transplanted to athymic nude mice were found elsewhere. The response of the tumor to CDDP was relevant to the dose administered. Regression of the tumor was observed when CDDP was administered at about 5 mg/kg/injection. The retardation of tumor growth was observed in the group to which CDDP was administered at about 2 mg/kg/injection. When CDDP was administered with In-111-labeled N-myc antisense oligonucleotides, regression of the tumor was observed in the group treated with In-111-labeled N-myc antisense oligonuclotides, and the retardation of tumor growth was observed in the group treated with In-111-labeled N-myc antisense oligonucleotides at the lower doses. These results indicate that CDDP enhances the antitumor effect of In-111-labeled N-myc antisense oligonucleotides against transplanted neuroblastoma in BALB/c athymic mice.