Development of Ad-mda7/IL-24-resistant lung cancer cell lines
dc.contributor.author | Pataer, Abujiang | |
dc.contributor.author | Chada, Sunil | |
dc.contributor.author | Roth, Jack A. | |
dc.contributor.author | Hunt, Kelly K. | |
dc.contributor.author | Swisher, Stephen G. | |
dc.date | 2022-08-11T08:08:57.000 | |
dc.date.accessioned | 2022-08-23T16:13:41Z | |
dc.date.available | 2022-08-23T16:13:41Z | |
dc.date.issued | 2007-12-07 | |
dc.date.submitted | 2008-09-08 | |
dc.identifier.citation | <p>Cancer Biol Ther. 2008 Jan;7(1):103-8. Epub 2007 Oct 13.</p> | |
dc.identifier.issn | 1555-8576 (Electronic) | |
dc.identifier.doi | 10.4161/cbt.7.1.5162 | |
dc.identifier.pmid | 18059175 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/33683 | |
dc.description.abstract | 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. | |
dc.language.iso | en_US | |
dc.relation | <p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18059175&dopt=Abstract">Link to Article in PubMed</a></p> | |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442784/ | |
dc.subject | Adenoviridae; Benzoquinones; Cell Line, Tumor; *Gene Therapy; Humans; Interleukins; Lactams, Macrocyclic; Lung Neoplasms; Proto-Oncogene Proteins c-akt; Receptors, Virus | |
dc.subject | Life Sciences | |
dc.subject | Medicine and Health Sciences | |
dc.title | Development of Ad-mda7/IL-24-resistant lung cancer cell lines | |
dc.type | Journal Article | |
dc.source.journaltitle | Cancer biology and therapy | |
dc.source.volume | 7 | |
dc.source.issue | 1 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/gsbs_sp/348 | |
dc.identifier.contextkey | 622933 | |
html.description.abstract | <p>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.</p> | |
dc.identifier.submissionpath | gsbs_sp/348 | |
dc.contributor.department | Graduate School of Biomedical Sciences | |
dc.source.pages | 103-8 |