A novel therapy for lung cancer targeting cancer stem cells.

一种针对癌症干细胞的肺癌新疗法。

• 批准号: 23591136
• 负责人: TAKIGUCHI Yuichi
• 金额: $ 3.33万
• 依托单位: Chiba 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-23591136/
• 关键词: メトホルミン; ゲフィチニブ; 癌幹細胞; 肺癌; 細胞株; アポトーシス; 細胞周期; シスプラチン

Cytotoxicity of metformin was elucidated in 4 human lung cancer cell lines. Colonogenicity and cell proliferation were inhibited by metformin in all the cell lines only when the cells were exposed to the metformin for a long period, suggesting its cytostatic characteristics. The combined effects of metformin and gefitinib were examined. It did not suppress the growth of already established tumors, nor did it augment tumor shrinkage by gefitinib. However, it significantly suppressed the regrowth of the tumor after effective treatment with gefitinib, suggesting metformin's specific effect on the residual cells. Its cytotoxicity was characterized by the absence of apoptosis induction and unremarkable cell cycle shift. The residual cells were characterized by enriched cells with high expression of CD133 and CD24. Metformin was still effective on this specific cell population. Targeting residual cells after chemotherapy might represent an effective new strategy for curing cancer.

在4种人肺癌细胞系中阐明了二甲双胍的细胞毒性。仅当细胞长时间暴露于二甲双胍时，二甲双胍才抑制所有细胞系的集落形成和细胞增殖，表明其具有细胞抑制特性。检查二甲双胍和吉非替尼的联合作用。它不抑制已经建立的肿瘤的生长，也不增加吉非替尼的肿瘤缩小。然而，在吉非替尼有效治疗后，它显著抑制了肿瘤的再生长，表明二甲双胍对残留细胞的特异性作用。其细胞毒性的特点是没有凋亡诱导和不显着的细胞周期偏移。残留细胞的特征在于具有高表达的CD 133和CD 24的富集细胞。二甲双胍对这种特定的细胞群仍然有效。靶向化疗后的残留细胞可能是治疗癌症的有效新策略。

项目成果

Targeting HDACs to overcome cisplatin resistance in malignant plural mesothelioma

靶向 HDAC 克服恶性多发性间皮瘤的顺铂耐药性

• 发表时间: 2013
• 作者: Baird A;Jennings C;McDonagh L;Flynn L;O'Donnell E;Barr M;Santoni-rugiu E;Hanse F;Kurz T;Takiguchi Y;Thomas W;Zimling Z;O'Byrne;K;Gray S
• 通讯作者: Gray S

Zoledronic acid, the third generation of bisphosphonates, produces anti-tumor effects on mesothelioma in vitro and in vivo through apoptosis or S phase arrest in p53-independent and RAS prenylation-independent manners.

唑来膦酸是第三代双膦酸盐，在体外和体内通过p53独立和RAS异戊二烯化独立方式的细胞凋亡或S期阻滞产生对间皮瘤的抗肿瘤作用。

• 发表时间: 2012
• 作者: Tada;Y;Li;Q;Kawamura;K;Kobayashi;H;Sekine;I;Takiguchi;Y;Tatsumi;K;Shimada;H;Hiroshima;K and Tagawa;M
• 通讯作者: M

Anti-proliferative action of metformin on various types of human lung cancer cell lines.

二甲双胍对各种类型的人肺癌细胞系的抗增殖作用。

• 发表时间: 2012
• 作者: Ashinuma H;et al
• 通讯作者: et al

Genome-wide cDNA microarray screening of genes related to pemetrexed resistance in mesothelioma cell lines

间皮瘤细胞系中培美曲塞耐药相关基因的全基因组 cDNA 微阵列筛选

• 发表时间: 2012
• 作者: Sekine I;Kitazono-Saitoh M;Kurimoto R;Sakaida E;Tada Y;Kurosu K;Tatsumi K;Takiguchi Y
• 通讯作者: Takiguchi Y

Expression of a murine homolog of apoptosis-inducing human IL-24/MDA-7 in murine tumors fails to induce apoptosis or produce anti-tumor effects

诱导细胞凋亡的人 IL-24/MDA-7 的鼠同源物在小鼠肿瘤中的表达未能诱导细胞凋亡或产生抗肿瘤作用

• 发表时间: 2012
• 期刊: Cellular Immunology
• 影响因子: 4.3
• 作者: Nagakawa;Hiroyasu;Shimozato;Osamu;Yu;Ling;Wada;Akihiko;Kawamura;Kiyoko;Li;Quanhai;Chada;Sunil;Tada;Yuji;Takiguchi;Yuichi;Tatsumi;Koichiro and Tagawa;Masatoshi
• 通讯作者: Masatoshi