Document Detail


Depletion of PI3K p85alpha induces cell cycle arrest and apoptosis in colorectal cancer cells.
MedLine Citation:
PMID:  19885597     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Colorectal cancer is one of the most common malignancies in the world. Overactivity of phosphatidylinositol 3-kinase (PI3K) is frequently detected in colorectal carcinoma. PI3K signaling plays a pivotal role in intracellular signal transduction pathways involved in cell growth, cellular transformation, and tumorigenesis. To specifically inhibit PI3K activity in colorectal cancer cells, we constructed a siRNA against the PI3K regulatory subunit p85alpha and transfected it into LoVo and SW480 cells. In the present study, treatment of colorectal cancer cells with PI3K p85alpha-specific siRNA inhibited cell proliferation, induced G1 phase cell cycle arrest and sensitized colorectal cancer cells to 5-FU-induced apoptosis. Furthermore, depletion of PI3K p85alpha resulted in significant activation of three Forkhead box class O (FoxO) transcription factors, which inhibited the expression of cyclin D1, cdk4 and induced expression of p27/Kip1. Activation of FoxO transcription factors also increased the expression of FasL. Thus, our results indicate that siRNA-mediated gene silencing of PI3K p85alpha may be a useful therapeutic strategy for colorectal carcinoma.
Authors:
Yan Sun; Shiyi Zhao; Hua Tian; Xiaoyun Xie; Faman Xiao; Kang Li; Yugang Song
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Oncology reports     Volume:  22     ISSN:  1791-2431     ISO Abbreviation:  Oncol. Rep.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-03     Completed Date:  2010-02-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9422756     Medline TA:  Oncol Rep     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1435-41     Citation Subset:  IM    
Affiliation:
Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / genetics*,  physiology*
Apoptosis*
Cell Cycle
Cell Line, Tumor
Cell Nucleus / metabolism
Cell Proliferation
Colorectal Neoplasms / genetics*,  metabolism*
Cyclin-Dependent Kinase Inhibitor p27 / metabolism
Cytoplasm / metabolism
Fas Ligand Protein / metabolism
Flow Cytometry / methods
Forkhead Transcription Factors / metabolism
Gene Expression Regulation, Neoplastic*
Humans
Phosphorylation
Chemical
Reg. No./Substance:
0/FASLG protein, human; 0/FOXO1 protein, human; 0/Fas Ligand Protein; 0/Forkhead Transcription Factors; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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