| Combination of telomerase antisense oligonucleotides simultaneously targeting hTR and hTERT produces synergism of inhibition of telomerase activity and growth in human colon cancer cell line. | |
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MedLine Citation:
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PMID: 15682468 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIM: To investigate synergism of inhibition of telomerase activity and proliferation of human colon cancer cells by combination of telomerase antisense oligonucleotides (ASODNs) simultaneously targeting human telomerase RNA (hTR) and human telomerase reverse transcriptase (hTERT) in vitro. METHODS: ASODN of hTR and ASODN of hTERT were transfected into human colon cancer SW480 cells by liposomal transfection reagents. Telomerase activity of SW480 cells was examined using telomeric repeat amplification protocol (TRAP)-enzyme-linked immunosorbent assay (PCR-ELISA). Proliferation activity of SW480 cells was tested by methyl thiazolyl tetrazolium assay. Apoptosis and cell cycle were analyzed by flow cytometry. RESULTS: The telomerase activity and cell survival rate in SW480 cells transfected with 0.2 mumol/L of ASODN of hTR or ASODN of hTERT for 24-72 h were significantly decreased in a time-dependent manner compared with those after treatment with sense oligonucleotides and untreated (telomerase activity: 24 h, 73%, 74% vs 99%, 98%; 48 h, 61%, 55% vs 98%, 99%; 72 h, 41%, 37% vs 99%, 97%; P<0.01; cell survival rate: 24 h, 88%, 86% vs 94%, 98%; 48 h, 49%, 47% vs 94%, 97%; 72 h, 44%, 42% vs 92%, 96%; P<0.01). Moreover, the telomerase activity and the cell survival rate in SW480 cells treated by the combination of telomerase anti-hTR and anti-hTERT were more significantly suppressed than single anti-hTR or anti-hTERT (telomerase activity: 24 h, 59% vs 73%, 74%; 48 h, 43% vs 61%, 55%; 72 h, 18% vs 41%, 37%; P<0.01; cell survival rate: 24 h, 64% vs 88%, 86%; 48 h, 37% vs 49%, 47%; 72 h, 25% vs 44%, 42%; P<0.01). Meanwhile, the apoptosis rates in the combination group were markedly increased compared with those in the single group (24 h, 18.0% vs 7.2%, 7.4%; 48 h, 23.0% vs 13.0%, 14.0%; 72 h, 28.6% vs 13.2%, 13.75; P<0.01). Cells in combination group were arrested at G(0)/G(1) phase. CONCLUSION: Telomerase anti-hRT and anti-hTERT suppress telomerase activity, and inhibit growth of human colon cancer cells probably via induction of apoptosis and retardation of cell cycle. Additionally, combined use of telomerase ASODNs targeting both hTR and hTERT yields synergistic action selective for human colon cancer. |
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Authors:
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Xiao-Hua Fu; Jian-Song Zhang; Na Zhang; Yang-De Zhang |
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Publication Detail:
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Type: In Vitro; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: World journal of gastroenterology : WJG Volume: 11 ISSN: 1007-9327 ISO Abbreviation: World J. Gastroenterol. Publication Date: 2005 Feb |
Date Detail:
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Created Date: 2005-01-31 Completed Date: 2005-03-16 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100883448 Medline TA: World J Gastroenterol Country: China |
Other Details:
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Languages: eng Pagination: 785-90 Citation Subset: IM |
Affiliation:
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Medical College, Hunan Normal University, Changsha 410006, Hunan Province, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Cell Division Cell Line, Tumor Cell Survival Colonic Neoplasms* DNA-Binding Proteins Gene Therapy / methods Humans Interphase Oligonucleotides, Antisense / pharmacology* Telomerase / genetics*, metabolism* Transfection |
| Chemical | |
Reg. No./Substance:
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0/DNA-Binding Proteins; 0/Oligonucleotides, Antisense; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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