| Antitumor effects of targeting hTERT lentivirus-mediated RNA interference against KB cell lines. | |
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MedLine Citation:
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PMID: 19806793 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Squamous cell carcinomas are the leading frequent malignant tumors in the oral and maxillofacial region. Currently available treatment options are of limited efficacy, and there is an urgent need for development of alternative therapies. RNA interference (RNAi) is a sequence-specific RNA degradation process. In this study, we screened and identified an in vitro-transcribed 21-bp shRNA targeting human telomerase reverse transcriptase (hTERT) from three candidates and generated a lentivirus vector. Subsequent experiments indicated that this lentiviral transgenic system could effectively transfer into target KB cells, above 80% gene transfer efficiency at MOI of 2.5, and significantly and specifically inhibited hTERT expression both in mRNA (73.42%) and protein (74.67-82.91%) levels. To further evaluate the role of hTERT-targeted RNAi, we found that hTERT inhibition consequently induced suppression of cyclin D1 (54.67%), upregulation of caspase-3 (100.10%), and caspase-9 (42.67%) of KB cells. Therefore, the apoptosis rates of KB cells were increased by 206.33%. In conclusion, these data indicated the potential of lentivirus vectors in cancer gene therapy, especially after development of more efficient vector production methods, and higher virus titers demonstrated that targeting hTERT RNAi may result in telomere uncapping, which triggers cell cycle arrest and apoptosis signal and leads to tumor suppression. |
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Authors:
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Dan Chen; Hongzhang Huang; Chaobin Pan; Jianguang Wang; Bin Zhang; Anxun Wang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Oncology research Volume: 17 ISSN: 0965-0407 ISO Abbreviation: Oncol. Res. Publication Date: 2009 |
Date Detail:
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Created Date: 2009-10-07 Completed Date: 2009-10-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9208097 Medline TA: Oncol Res Country: United States |
Other Details:
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Languages: eng Pagination: 621-30 Citation Subset: IM |
Affiliation:
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Department of Oral & Maxillofacial Surgery, Guanghua College of Stomatology, Sun Yat-Sen University, Guangzhou, Guangdong Province, 510055, PR China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis Carcinoma, Squamous Cell / therapy* Gene Therapy* Humans KB Cells Lentivirus / genetics* Mouth Neoplasms / therapy* RNA Interference* RNA, Messenger / analysis Telomerase / analysis, antagonists & inhibitors*, genetics Transduction, Genetic |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; EC 2.7.7.49/TERT protein, human; EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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