Journal
LUNG CANCER
Volume 58, Issue 1, Pages 21-29Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.lungcan.2007.05.013
Keywords
Sirt1; antisense oligonucleotides; apoptosis; ionizing radiation
Categories
Ask authors/readers for more resources
Sirt1, a conserved nicotinamide adenine dinucteotide (NAD(+))-dependent deacetylase, has been implicated in modulating transcriptional silencing and cell survival, and seems to play a key role in carcinogenesis through deacetytation of important regulatory proteins. This makes it a potential target in cancer therapy. The purpose of this study was to determine whether inhibition of Sirt1 by using antisense oligonucleotides (ASODN) induces apoptosis and enhances radiation sensitization in A549 lung cancer cells. Initially, transient transfection of A549 lung cancer cells with ASODN against Sirt1 specifically reduced Sirt1 expression in a dose-dependent and sequence-specific manner, at both mRNA and proteins levels. The inhibition of Sirt1 obviously decreased A549 cells survival, induced G1 arrest as well as apoptosis. Furthermore, the inhibition of Sirt1 by ASODN greatly increased radiation-induced antiprotiferation effects involving in increasing acetylation of tumour suppressor p53 and Bax expression in A549 lung cancer cells. In summary, our results indicate that downregulation of Sirt1 by ASODN decreases survival and increases radiation-induced antiproliferation effects of human lung cancer cells and suggest that inhibition of Sirt1 by ASODN may be a potential gene therapy approach to the treatment of lung cancer. (c) 2007 Elsevier Ireland Ltd. All. rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available