Targeted therapy for cancer stem-like cells of non-small cell lung cancers with inhibition of the cJun transcription factor

抑制cJun转录因子的非小细胞肺癌干细胞样细胞靶向治疗

• 批准号: 23591132
• 负责人: KINOSHITA Ichiro
• 金额: $ 3.33万
• 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: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591132/
• 关键词: 肺癌; 癌幹細胞; ｃJun; EZH2; 幹細胞; cJun; HDAC; エピジェネティクス; 分子標的薬

Sphere forming capacity under serum-free culture, indicative of cancer stem cells, were decreased by cJun inhibition in non-small lung cancer (NSCLC) cells, while sphere forming cells did not show enhanced tumorigenicity in SCID mice.Meanwhile, an inhibitor of histone methyltransferase EZH2 involved in stem cell maintenance via epigenetic regulation suppressed growth of NSCLC cells. An inhibitor of histone deacetylase (HDAC), another epigenetic regulator, showed a synergistic growth suppressive effect with the EZH2 inhibitor. Combined epigenetic therapy with an EZH2 inhibitor and an HDAC inhibitor may represent an effective approach for NSCLCs.

在非小细胞肺癌（NSCLC）细胞中，cJun抑制剂降低了无血清培养条件下肿瘤干细胞的球体形成能力，而在SCID小鼠中，球体形成细胞的致瘤性没有增强。同时，通过表观遗传调控参与干细胞维持的组蛋白甲基转移酶EZH2抑制剂抑制了NSCLC细胞的生长。另一种表观遗传调节剂组蛋白脱乙酰酶（HDAC）的抑制剂与EZH2抑制剂显示出协同的生长抑制作用。EZH2抑制剂和HDAC抑制剂的联合表观遗传疗法可能代表了NSCLC的有效方法。

项目成果

CD133 expression: a potential prognostic marker for non-small cell lung cancers

• DOI: 10.1007/s10147-013-0541-x
• 发表时间: 2014-04-01
• 期刊: INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY
• 影响因子: 3.3
• 作者: Mizugaki, Hidenori;Sakakibara-Konishi, Jun;Nishimura, Masaharu
• 通讯作者: Nishimura, Masaharu

Expression of LGR5, an intestinal stem cell marker, during each stage of colorectal tumorigenesis.

LGR5（一种肠道干细胞标记物）在结直肠肿瘤发生的各个阶段的表达。

• 发表时间: 2011
• 期刊: Anticancer Research
• 影响因子: 2
• 作者: Kayoko Takeda;I. Kinoshita;Y. Shimizu;Y. Matsuno;T. Shichinohe;H. Dosaka
• 通讯作者: H. Dosaka

Effects of combined epigenetic therapy with the histone methyltransferase EZH2 inhibitor 3-deazaneplanocin and the histone deacetylase inhibitor SAHA on non-small cell lung cancer cells

组蛋白甲基转移酶EZH2抑制剂3-deazaneplanocin和组蛋白脱乙酰酶抑制剂SAHA联合表观遗传学治疗对非小细胞肺癌细胞的影响

• 作者: Takashina T;Kinoshita I;Kikuchi J;Shimizu Y;Konishi JS;Oizumi S;Nishimura M and Dosaka-Akita H
• 通讯作者: Nishimura M and Dosaka-Akita H

Cancer stem-like cells derived from chemoresistant tumors have a unique capacity to prime tumorigenic myeloid cells.

• DOI: 10.1158/0008-5472.can-13-2169
• 发表时间: 2014-05
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: T. Yamashina;Muhammad Baghdadi;A. Yoneda;I. Kinoshita;S. Suzu;H. Dosaka-akita;M. Jinushi

EZH2阻害薬とヒストン脱アセチル化酵素阻害薬の併用療法の非小細胞肺癌細胞に対する抗腫瘍効果の検討

EZH2抑制剂与组蛋白脱乙酰酶抑制剂联合治疗对非小细胞肺癌细胞的抗肿瘤作用考察

• 作者: 高階太一;木下一郎;菊地順子;池澤靖元;榊原純;大泉聡史;西村正治;秋田弘俊
• 通讯作者: 秋田弘俊