Document Detail


RNA interference (RNAi) of Ufd1 protein can sensitize a hydroxycamptothecin-resistant colon cancer cell line SW1116/HCPT to hydroxycamptothecin.
MedLine Citation:
PMID:  21401896     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
OBJECTIVE:   To investigate whether RNA interference (RNAi) of the ubiquitin fusion-degradation 1-like protein (Ufd1) could sensitize hydroxycamptothecin (HCPT)-resistant colon cancer cell line SW1116/HCPT to the cytotoxic effect of HCPT.
METHODS:   SW1116/HCPT cells were transfected with plasmids containing Ufd1-specific small interfering RNA (siRNA) (Ufd1 knockdown cells) and non-specific siRNA (control cells). A drug sensitivity analysis, 3-(4,5)-dimethylthiahiazol (-z-y1)-3,5-di- phenytetrazoliumromide (MTT) assay was performed on Ufd1 knockdown cells and control cells. After treating the cells with HCPT, a caspase-3 and caspase-4 activity assay, flow cytometric analysis and Western blot for detecting phosphorylated c-Jun N-terminal kinase (p-JNK), phosphorylated protein kinases B (p-Akt), P53, ubiquitin, GADD 153 and Grp78/Bip were performed.
RESULTS:   According to the MTT assay, the survival rate of knockdown cells was significantly lower than that of the control cells (P < 0.01). Both caspase-3 and caspase-4 activity assay showed higher activation level in Ufd1 knockdown cells than that in the control cells (P < 0.01). A flow cytometric analysis revealed more severe S-phase arrest in the Ufd1 knockdown cells than that in the control cells (P < 0.05). The Western blot showed that increasing the concentration of HCPT resulted in a higher expression level of p-JNK, P53, ubiquitin, GADD 153 and Grp78/Bip in the Ufd1 knockdown cells than that in the control cells.
CONCLUSION:   Ufd1 plays a key role in HCPT resistance of SW1116/HCPT and RNAi of Ufd1 can sensitize SW1116/HCPT to the cytotoxic effect of HCPT via strengthening the activation of caspase-3 pathway and disturbing endoplasmic reticulum functions.
Authors:
Xiang Chen; Zhi Hua Ran; Jin Lu Tong; Fang Nie; Ming Ming Zhu; Xi Tao Xu; Shu Dong Xiao
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of digestive diseases     Volume:  12     ISSN:  1751-2980     ISO Abbreviation:  J Dig Dis     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-15     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101302699     Medline TA:  J Dig Dis     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  110-6     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. Journal of Digestive Diseases © 2011 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.
Affiliation:
Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai, China.
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