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阿片类拮抗剂对裸鼠体内小鼠神经母细胞瘤的调节作用。

Modulation of murine neuroblastoma in nude mice by opioid antagonists.

作者信息

Zagon I S, McLaughlin P J

出版信息

J Natl Cancer Inst. 1987 Jan;78(1):141-7. doi: 10.1093/jnci/78.1.141.

DOI:10.1093/jnci/78.1.141
PMID:3025501
Abstract

Naltrexone, an opioid antagonist, had an inhibitory effect on the growth of murine S20Y neuroblastoma in BALB/c nude mice. Daily injections of 0.1 mg naltrexone/kg, which invoked a receptor blockade for 6-8 hours/day, resulted in 31-92% delay in latency time prior to tumor expression and a 27-49% increase in mean survival time; the magnitude of antitumor response was governed by tumor burden. Inoculation of neuroblastoma (10(6)-2.5 X 10(4) cells) resulted in measurable tumors in 10-13 days and mean survival times of 30-34 days. Immunoreactive beta-endorphin was detected in tumor tissue (39.7 pg/mg protein). Receptor binding assays revealed specific saturable binding of ligands related to delta- and kappa-binding sites, but not for the mu-binding site. These results demonstrate that opioid antagonist modulation of neuro-oncogenesis is not dependent on the integrity of T-cell-mediated immunity and suggest the feasibility of utilizing the nude mouse model in exploring the role of endogenous opioids in human cancers.

摘要

纳曲酮是一种阿片类拮抗剂,对BALB/c裸鼠体内的小鼠S20Y神经母细胞瘤生长具有抑制作用。每天注射0.1毫克/千克纳曲酮,可引发6 - 8小时/天的受体阻滞,导致肿瘤出现前的潜伏期延迟31 - 92%,平均生存时间增加27 - 49%;抗肿瘤反应的程度受肿瘤负荷的影响。接种神经母细胞瘤(10⁶ - 2.5×10⁴个细胞)在10 - 13天内产生可测量的肿瘤,平均生存时间为30 - 34天。在肿瘤组织中检测到免疫反应性β-内啡肽(39.7皮克/毫克蛋白质)。受体结合试验显示与δ和κ结合位点相关的配体具有特异性饱和结合,但与μ结合位点无关。这些结果表明,阿片类拮抗剂对神经肿瘤发生的调节不依赖于T细胞介导的免疫完整性,并提示利用裸鼠模型探索内源性阿片类物质在人类癌症中的作用的可行性。

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