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，使它们对恶性肿瘤具有可能的治疗效用。本文观察了~（111）In标记的N-myc反义寡核苷酸与顺铂（CDDP）联合应用对BALB/c裸鼠腹腔移植人神经母细胞瘤的抗肿瘤作用。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无胸腺裸鼠的作用在别处被发现。肿瘤对CDDP的反应与给药剂量有关。当以约5 mg/kg/注射施用CDDP时，观察到肿瘤消退。在以约2 mg/kg/注射施用CDDP的组中观察到肿瘤生长的延迟。当CDDP与In-111标记的N-myc反义寡核苷酸一起给药时，在用In-111标记的N-myc反义寡核苷酸治疗的组中观察到肿瘤消退，并且在用In-111标记的N-myc反义寡核苷酸以较低剂量治疗的组中观察到肿瘤生长的延迟。这些结果表明，CDDP增强In-111标记的N-myc反义寡核苷酸对BALB/c裸鼠移植性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.