Document Detail


Cyclopamine Blocked the Growth of Colorectal Cancer SW116 Cells by Modulating Some Target Genes of Gli1 in vitro.
MedLine Citation:
PMID:  21940310     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Background/Aims: Hedgehog (Hh) pathway has been considered as a therapy target for various cancer entities. However, its mechanism in colorectal cancer is still unclear. Methodology: We analyzed the expression of Hh pathway members in colorectal adenomas and cancer cell lines and then studied its relationship with survival of colorectal cancer cells through inhibiting Hh pathway by cyclopamine. Moreover, we studied the regulation of Gli1 on insulin-like growth factor binding protein 6 (IGFBP6) and B-cell CLL/lymphoma 2 (Bcl-2) genes at the level of transcription by XChIP and cyclopamine inhibition assay. Results: Sonic hedgehog (Shh), Smoothened (Smo), patched (Ptch) and Gli1 genes mRNA were expressed in SW116 cells. Gli1 bound to promoter regions of Bcl-2 and IGFBP6 genes, cyclopamine inhibited proliferation and induced apoptosis through inhibiting the transcriptions of IGFBP6 (p=0.003), proliferating cell nuclear antigen (PCNA) (p=0.014) and Bcl-2 (p=0.013), and increasing that of BCL2-associated X protein (Bax) and BCL2-antagonist/killer 1 (Bak1) (p=0.003 and 0.001, respectively) in SW116 cells. Conclusions: Hh pathway is aberrant activation in part colorectal carcinomas cell lines and its inhibitor may be an effectual agent for colorectal cancer chemoprevention. It may be one of the mechanisms that Gli1 maintained cell survival by binding the promoter regions and facilitating transcription of IGFBP6 and Bcl-2 genes.
Authors:
Jian-Ye Wu; Xuan-Fu Xu; Ling Xu; Pei-Qin Niu; Feng Wang; Guo-Yong Hu; Xing-Peng Wang; Chuan-Yong Guo
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-15
Journal Detail:
Title:  Hepato-gastroenterology     Volume:  58     ISSN:  0172-6390     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-9-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8007849     Medline TA:  Hepatogastroenterology     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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