Authors: Chen, Dan; Huang, Hongzhang; Pan, Chaobin; Wang, Jianguang; Zhang, Bin; Wang, Anxun

Source: Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, Volume 17, Numbers 11-12, 2009 , pp. 621-630(10)

Publisher: Cognizant Communication Corporation

Abstract:

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.

Keywords: RNA interference (RNAi); Gene therapy; Oral squamous cell carcinoma; Human telomerase reverse transcriptase; Lentiviral vector

Document Type: Research article

DOI: http://dx.doi.org/10.3727/096504009789745548

Publication date: 2009-11-01

More about this publication?

• Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
  Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.

Related content

• In this: publication
• By this: publisher
• In this Subject: Oncology
• By this author: Chen, Dan ;  Huang, Hongzhang ;  Pan, Chaobin ;  Wang, Jianguang ;  Zhang, Bin ;  Wang, Anxun

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers