UMass Chan Affiliations
Graduate School of Biomedical SciencesDocument Type
Journal ArticlePublication Date
2007-12-07Keywords
Adenoviridae; Benzoquinones; Cell Line, Tumor; *Gene Therapy; Humans; Interleukins; Lactams, Macrocyclic; Lung Neoplasms; Proto-Oncogene Proteins c-akt; Receptors, VirusLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Many cancers can become resistant to repeated administration of even the most effective therapeutic agents. In developing adenoviral mda-7/IL-24 (Ad-mda-7/IL-24) therapy for lung cancer, we have anticipated this potential clinical problem by attempting to identify the molecular mechanisms of Ad-mda7/IL-24 resistance in several Ad-mda7/IL-24-resistant lung cancer cell lines that we have developed. For the present study, we established four Admda7- resistant cell lines by repeated selection of resistant clones of parental Ad-mda7-sensitive A549 cells: two lines (A549R1 and A549R2) resistant to both adenoviral vector and the mda-7 gene and two (A549R3 and A549R4) resistant to the therapeutic mda-7 gene only. As shown by western blot analysis of several known anti-apoptotic proteins, parental A549 and resistant A549R3 cells expressed similar levels of AKT and phosphorylated AKT (p-AKT), whereas resistant A549R3 and A549R4 cells expressed higher levels of bcl-2 and lower levels of bcl-xL than did their parental cells. As shown by flow-cytometric analysis, treating resistant A549R3 and A549R4 cells with a combination of Ad-mda7 and 17-allyl-amino-17-demethoxygeldanamycin (17AAG) (50 nM) for 48 hours enhanced apoptosis. Together, these in vitro findings indicate that an antiapoptotic mechanism may underlie Ad-mda7 resistance and that such resistance can be overcome by addition of 17AAG. Further investigations along these lines are warranted.Source
Cancer Biol Ther. 2008 Jan;7(1):103-8. Epub 2007 Oct 13.
DOI
10.4161/cbt.7.1.5162Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33683PubMed ID
18059175Related Resources
ae974a485f413a2113503eed53cd6c53
10.4161/cbt.7.1.5162