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Doxorubicin enhances the expression of transgene under control of the CMV promoter in anaplastic thyroid carcinoma cells

Cited 26 time in Web of Science Cited 30 time in Scopus
Authors
Kim, Kwang Il; Kang, Joo Hyun; Chung, June-Key; Lee, Yong Jin; Jeong, Jae Min; Lee, Dong Soo; Lee, Myung Chul
Issue Date
2007
Publisher
Society of Nuclear Medicine
Citation
J Nucl Med. 2007;48:1553-1561
Keywords
AnimalsAntibiotics, Antineoplastic/*therapeutic useCell Line, TumorCombined Modality TherapyCytomegalovirus/geneticsDoxorubicin/*therapeutic use*Gene TherapyHumansI-kappa B Proteins/metabolismIodine Radioisotopes/*therapeutic useMaleMiceMice, NudePromoter Regions, GeneticRadiotherapy, AdjuvantSymporters/*biosynthesis/geneticsThyroid Neoplasms/drug therapy/*metabolism/*radiotherapyTransfectionTransgenes
Abstract
We investigated the effect of doxorubicin on transgene expression and evaluated the mechanism of enhanced transgene expression by doxorubicin in transfected human anaplastic thyroid cancer cells (ARO cells). METHODS: ARO cells were transfected with plasmid vectors or adenoviral vectors expressing human sodium/iodide symporter (hNIS) or luciferase (Luc) under the control of cytomegalovirus (CMV) promoter. After treating transfected and control ARO cells with doxorubicin, iodide uptake assay and luciferase assay were performed. Reversed-phase polymerase chain reaction analysis for hNIS and Western blot analysis for IkappaB protein were executed. Electrophoretic mobility-shift assay (EMSA) was performed to evaluate nuclear factor-kappaB (NF-kappaB) binding activity induced by doxorubicin. Scintigraphic and bioluminescent images were acquired and quantitated before and after doxorubicin in a tumor-bearing mouse model. RESULTS: Radioiodide uptake in ARO cells transfected with the NIS gene under the CMV promoter was remarkably enhanced by doxorubicin, and this corresponded to a significant increase in NIS messenger RNA. In addition, luciferase gene upregulation by doxorubicin was also observed in luciferase gene transfected ARO cells. These results were verified by in vivo imaging in a tumor-bearing mouse model. Moreover, transgene expressional enhancement by doxorubicin was observed after transfecting ARO cells with adenoviral vector or plasmid vector, when transgenes were under the control of a CMV promoter. In addition, NF-kappaB, activated by doxorubicin, induced transgene transcription under the control of the CMV promoter, which possesses an NF-kappaB binding site. CONCLUSION: These findings indicate that doxorubicin enhances transgene expression under the control of the CMV promoter and that doxorubicin might be used as an adjuvant to radioiodine therapy by NIS gene transfer in anaplastic thyroid carcinoma.
ISSN
0161-5505 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17704247

http://hdl.handle.net/10371/10480
DOI
https://doi.org/10.2967/jnumed.106.038612
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Radiation Applied Life Science (대학원 협동과정 방사선응용생명과학전공)Journal Papers (저널논문_방사선응용생명과학전공)
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