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. British Journal of Cancer (2011) 105, 212-220. doi: 10.1038/bjc.2011.200 www.bjcancer.com Published online 21 June 2011 (C) 2011 Cancer Research UK
基金:
NIH [R03CA137479-01A1]; National Natural Science Foundation of China [81001005]
第一作者单位:[1]Ohio State Univ, Nationwide Childrens Hosp, Coll Med, Dept Pediat,Res Inst,Ctr Childhood Canc, Columbus, OH 43205 USA[2]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Internal Med,Div Cardiol, Wuhan 430030, Peoples R China
通讯作者:
推荐引用方式(GB/T 7714):
Lin L.,Liu Y.,Li H.,et al.Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030[J].BRITISH JOURNAL OF CANCER.2011,105(2):212-220.doi:10.1038/bjc.2011.200.
APA:
Lin, L.,Liu, Y.,Li, H.,Li, P-K,Fuchs, J....&Lin, J..(2011).Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030.BRITISH JOURNAL OF CANCER,105,(2)
MLA:
Lin, L.,et al."Targeting colon cancer stem cells using a new curcumin analogue, GO-Y030".BRITISH JOURNAL OF CANCER 105..2(2011):212-220