Document Detail


Effects of phosphorothioate anti-sense oligodeoxynucleotides on colorectal cancer cell growth and telomerase activity.
MedLine Citation:
PMID:  15526364     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
AIM: To investigate the inhibitory effect of phosphorothioate anti-sense oligodeoxynucleotides (PASODN) on colorectal cancer LS-174T cells in vitro and the mechanism of inhibition of telomerase activity in these cells. METHODS: PASODN were used to infect LS-174T cells and block human telomerase RNA (hTR) through anti-sense technology. The inhibitory effect of PASODN was evaluated by colony-forming inhibition assay and growth curve. Changes of telomerase activity in LS-174T cells were detected by polymerase chain reaction-enzyme-linked immunosorbent assay (PCR-ELISA), and the level of apoptosis was analyzed by flow cytometry (FCM) assay. RESULTS: PASODN showed a dose and time-dependent inhibition of cell proliferation. The optimal dosage of PASODN was 10 mumol/L. The colony-forming efficiency was 10.3% in PASODN group after 10 d, whereas that in phosphorothioate mis-sense oligodeoxynucleotides (PMSODN) group with the same concentration and in PBS group (blank control) was 49.1% and 50.7%, respectively. PCR-ELISA results indicated that telomerase activity in the PASODN group was obviously inhibited in comparison with in the control groups (P<0.01, t = 3.317 and 3.241, t0.01(20) = 2.845). Meanwhile, before the number of cells was decreased, the morphological changes were observed in the cells of PASODN group. The cells in PASODN group showed the apoptotic peak at 72 h after infection, whereas the control group did not show. CONCLUSION: Specific sequence oligonucleotides can inhibit telomerase activity and lead to cell apoptosis, suggesting a novel treatment strategy for malignant tumors induced by telomerase.
Authors:
Xi-Shan Wang; Kuan Wang; Xue Li; Song-Bin Fu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  World journal of gastroenterology : WJG     Volume:  10     ISSN:  1007-9327     ISO Abbreviation:  World J. Gastroenterol.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-11-04     Completed Date:  2005-01-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  100883448     Medline TA:  World J Gastroenterol     Country:  China    
Other Details:
Languages:  eng     Pagination:  3455-8     Citation Subset:  IM    
Affiliation:
Department of Abdominal Surgery, Tumour Hospital of Harbin Medical University, Harbin 150040, Heilongjiang Province, China. 1966120808@sina.com
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MeSH Terms
Descriptor/Qualifier:
Apoptosis
Cell Division
Cell Line, Tumor / cytology
Colorectal Neoplasms*
Enzyme Activation / genetics
Flow Cytometry
Humans
Neoplastic Stem Cells
Oligodeoxyribonucleotides, Antisense / pharmacology*
Telomerase / metabolism*
Thionucleotides / pharmacology*
Chemical
Reg. No./Substance:
0/Oligodeoxyribonucleotides, Antisense; 0/Thionucleotides; EC 2.7.7.49/Telomerase

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