Therapy of Lung Cancer Based on the Regulation of Gene Expression

基于基因表达调控的肺癌治疗

• 批准号: 08670640
• 负责人: AKITA Hirotoshi
• 金额: $ 1.41万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670640/
• 关键词: Lung Cancer; Gene Expression; Antisense; Retinoic Acid

The overexpression of c-myc frequently accmpanies the relapse of small cell lung cancers (SCLCs) and contributes to the poor prognosis of patients with SCLVs. In this tudy, We investigated whether c-myc antisense oligodeoxynucleoside phosphorothioate (OPT) used in combination with all-trans-retinoic acid (RA) could be an experimental therapeutic tool against c-myc in a SCLC cell lime, NCI-H82, overexpressing c-myc with amplification of this gene. A c-myc antisense OPT covering the translational initiation site of c-myc mRNA decreased c-myc expression and inhibited cell growth. AII-trans RA also down-regulated c-myc expression as well as cell growth, as was previously reported. A combination of this antisenes DNA with all-trans-RA exhibited a enhanced reduction of c-myc expression over either agent given alone. Furthermore, this combination showed a greater inhibition of cell growth through c-myc down-regulation than either agent alone.These data suggest that c-myc antisense DNA in combination with RA may represent an attractive modality of gene regulation-based therapy of SCLCs in future, although further efforts are needed for the more potent down-regulation of c-myc.

c-myc基因的过度表达常促进小细胞肺癌（SCLC）的复发，并导致SCLV患者预后不良。在本研究中，我们研究了c-myc反义寡脱氧核苷硫代磷酸酯（OPT）与全反式维甲酸（RA）联合使用是否可以成为一种实验性治疗工具，在SCLC细胞系NCI-H82中，过度表达c-myc并扩增该基因。c-myc反义OPT覆盖c-myc mRNA的翻译起始位点，降低c-myc表达，抑制细胞生长。全反式RA也下调c-myc的表达以及细胞生长，如以前报道的。这种反义DNA与全反式-RA的组合表现出增强的c-myc表达的减少比单独给予任何一种药物。此外，这种组合表现出更大的抑制细胞生长，通过c-myc下调比任何单独agents.These数据表明，c-myc反义DNA与RA的组合可能代表一个有吸引力的模式，基因调控为基础的治疗SCLC在未来，虽然需要进一步的努力，更有力的下调c-myc。