槲寄生凝集素抑制 Myc 扩增的小细胞肺癌的生长。

Mistletoe lectin inhibits growth of Myc-amplified small-cell lung cancer.

机构信息

Division of Pulmonary, Critical Care and Sleep Medicine, Case Western Reserve University, The Louis Stokes Cleveland VA Medical Center and Case Comprehensive Cancer Center, Ohio, Cleveland, USA.

Case Comprehensive Cancer Center, Case Western Reserve University, Ohio, Cleveland, USA.

出版信息

Cancer Med. 2023 Apr;12(7):8378-8387. doi: 10.1002/cam4.5558. Epub 2022 Dec 23.

DOI:10.1002/cam4.5558

PMID:36562288

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10134353/

Abstract

BACKGROUND

Small-cell lung cancer (SCLC) is the deadliest form of lung cancer but lacks targeted therapies.

METHODS

We studied the effect of the natural product mistletoe lectin (ML) in pre-clinical models of SCLC, focusing on cell lines with amplification of the myc family oncogenes C-myc and N-myc.

RESULTS

We found that ML treatment inhibits growth of SCLC cell lines in culture and induces apoptosis. ML treatment also decreases the expression of the amplified myc proteins. Over-expression of either C-myc or N-myc results in enhanced SCLC cell sensitivity to ML. In a mouse xenograft model of SCLC, treatment with ML results in decreased tumor growth over 4 weeks with evidence of increased apoptosis in tumors from treated animals.

CONCLUSION

Overall, our results demonstrate that ML exhibits therapeutic potential in SCLC, that is at least partially dependent on myc protein expression.

摘要

背景

小细胞肺癌（SCLC）是肺癌中最致命的一种，但缺乏靶向治疗方法。

方法

我们研究了天然产物槲寄生凝集素（ML）在 SCLC 的临床前模型中的作用，重点研究了 myc 家族癌基因 C-myc 和 N-myc 扩增的细胞系。

结果

我们发现 ML 治疗可抑制 SCLC 细胞系在培养中的生长并诱导细胞凋亡。ML 治疗还降低了扩增 myc 蛋白的表达。过表达 C-myc 或 N-myc 均可使 SCLC 细胞对 ML 更加敏感。在 SCLC 的小鼠异种移植模型中，用 ML 治疗可在 4 周内减少肿瘤生长，并在来自治疗动物的肿瘤中显示出增加的细胞凋亡的证据。