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dc.contributor.authorPataer, Abujiang
dc.contributor.authorChada, Sunil
dc.contributor.authorRoth, Jack A.
dc.contributor.authorHunt, Kelly K.
dc.contributor.authorSwisher, Stephen G.
dc.date2022-08-11T08:08:57.000
dc.date.accessioned2022-08-23T16:13:41Z
dc.date.available2022-08-23T16:13:41Z
dc.date.issued2007-12-07
dc.date.submitted2008-09-08
dc.identifier.citation<p>Cancer Biol Ther. 2008 Jan;7(1):103-8. Epub 2007 Oct 13.</p>
dc.identifier.issn1555-8576 (Electronic)
dc.identifier.doi10.4161/cbt.7.1.5162
dc.identifier.pmid18059175
dc.identifier.urihttp://hdl.handle.net/20.500.14038/33683
dc.description.abstractMany 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.isoen_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.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3442784/
dc.subjectAdenoviridae; Benzoquinones; Cell Line, Tumor; *Gene Therapy; Humans; Interleukins; Lactams, Macrocyclic; Lung Neoplasms; Proto-Oncogene Proteins c-akt; Receptors, Virus
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleDevelopment of Ad-mda7/IL-24-resistant lung cancer cell lines
dc.typeJournal Article
dc.source.journaltitleCancer biology and therapy
dc.source.volume7
dc.source.issue1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/348
dc.identifier.contextkey622933
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.submissionpathgsbs_sp/348
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages103-8


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