Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030.
Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030.
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使用新型姜黄素类似物 GO-Y030 靶向结肠癌干细胞
DOI：
10.1038/bjc.2011.200
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发表时间：
2011-07-12
影响因子：
8.8
通讯作者：
Lin, J.
中科院分区：
文献类型：
--
作者：
Lin, L.;Liu, Y.;Li, H.;Li, P-K;Fuchs, J.;Shibata, H.;Iwabuchi, Y.;Lin, J.
背景：信号转导和转录激活因子3（STAT 3）的持续激活在包括结肠癌在内的许多类型的癌症中常见。到目前为止，STAT 3是否被激活和STAT 3抑制的影响，新开发的姜黄素类似物，GO-Y 030，在结肠癌stemcells.Methods：流式细胞术被用来分离结肠癌干细胞，其特征在于由醛脱氢酶（ALDH）阳性和CD 133阳性亚群（ALDH+/CD 133+）。STAT 3的磷酸化水平和STAT 3的抑制作用，由一个新开发的姜黄素类似物，GO-Y 030，靶向STAT 3在结肠癌干细胞examined.Results：我们的研究结果观察到，ALDH+/CD 133+结肠癌细胞表达更高水平的磷酸化STAT 3比ALDH阴性/CD 133阴性结肠癌细胞，表明STAT 3在结肠癌干细胞中被激活。GO-Y 030和姜黄素抑制结肠癌干细胞中STAT 3磷酸化、细胞活力、肿瘤球形成。GO-Y 030还降低了STAT 3下游靶基因的表达，并诱导结肠癌干细胞的凋亡。此外，GO-Y 030抑制肿瘤生长的肿瘤干细胞从两个SW 480和HCT-116结肠癌细胞系在小鼠model.Conclusion：我们的研究结果表明，STAT 3是一个新的治疗靶点在结肠癌干细胞，和抑制激活的STAT 3在肿瘤干细胞中的GO-Y 030可能提供一个有效的治疗结直肠癌。
Background:Persistent activation of signal transducers and activators of transcription 3 (STAT3) is commonly detected in many types of cancer, including colon cancer. To date, whether STAT3 is activated and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, in colon cancer stem cells are still unknown.Methods:Flow cytometry was used to isolate colon cancer stem cells, which are characterised by both aldehyde dehydrogenase (ALDH)-positive and CD133-positive subpopulations (ALDH+/CD133+). The levels of STAT3 phosphorylation and the effects of STAT3 inhibition by a newly developed curcumin analogue, GO-Y030, that targets STAT3 in colon cancer stem cells were examined.Results:Our results observed that ALDH+/CD133+ colon cancer cells expressed higher levels of phosphorylated STAT3 than ALDH-negative/CD133-negative colon cancer cells, suggesting that STAT3 is activated in colon cancer stem cells. GO-Y030 and curcumin inhibited STAT3 phosphorylation, cell viability, tumoursphere formation in colon cancer stem cells. GO-Y030 also reduced STAT3 downstream target gene expression and induced apoptosis in colon cancer stem cells. Furthermore, GO-Y030 suppressed tumour growth of cancer stem cells from both SW480 and HCT-116 colon cancer cell lines in the mouse model.Conclusion:Our results indicate that STAT3 is a novel therapeutic target in colon cancer stem cells, and inhibition of activated STAT3 in cancer stem cells by GO-Y030 may offer an effective treatment for colorectal cancer.
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影响因子：
11.2
作者：
Huang EH;Hynes MJ;Zhang T;Ginestier C;Dontu G;Appelman H;Fields JZ;Wicha MS;Boman BM
通讯作者：
Boman BM
DOI：
10.1186/bcr920
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Dontu G;Jackson KW;McNicholas E;Kawamura MJ;Abdallah WM;Wicha MS
通讯作者：
Wicha MS
DOI：
10.1073/pnas.0703478104
发表时间：
2007-06-12
影响因子：
11.1
作者：
Dalerba, Piero;Dylla, Scott J.;Clarke, Michael F.
通讯作者：
Clarke, Michael F.
影响因子：
11.5
作者：
Diaz, N;Minton, S;Muro-Cacho, CA
通讯作者：
Muro-Cacho, CA
DOI：
10.1016/s0022-2143(97)90107-4
发表时间：
1997-12-01
期刊：
JOURNAL OF LABORATORY AND CLINICAL MEDICINE
影响因子：
--
作者：
Hanif, R;Qiao, L;Rigas, B
通讯作者：
Rigas, B