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    
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.
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.
Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai, China.
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