Adenovirus vector-mediated perforin expression driven by a glucocorticoid-inducible promoter inhibits tumor growth in vivo.
To evaluate the concept that in vivo transfer of perforin complementary DNA (cDNA) will suppress tumor growth, we constructed an adenovirus vector (AdGRE.PFP) carrying perforin cDNA driven by the glucocorticoid response element (GRE) promoter. We infected A549 lung carcinoma cells with this vector in vitro and in vivo, and evaluated cell growth over time. In the presence of dexamethasone, in vitro infection of A549 cells with the AdGRE.PFP vector yielded perforin messenger RNA (mRNA) transcripts and effectively suppressed A549 cell growth. In accord with these in vitro observations, administration of dexamethasone following direct injection of AdGRE. PFP into established subcutaneous A549 tumors in nude mice resulted in a marked reduction in tumor growth as compared with AdGRE.PFP infection without dexamethasone or with dexamethasone alone. These observations suggest that regulable, adenovirus-mediated gene expression of perforin cDNA may have potential as a strategy for local control of tumor cell growth.
Narumi
K
K
Division of Pulmonary and Critical Care Medicine, New York Hospital-Cornell Medical Center, New York, New York, USA.
Kojima
A
A
Crystal
R G
RG
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D016923:Cell Death; D002455:Cell Division; D003907:Dexamethasone / Q000494:pharmacology; D005822:Genetic Vectors; D005938:Glucocorticoids / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D011401:Promoter Regions, Genetic; D013602:T-Lymphocytes, Cytotoxic; D014407:Tumor Cells, Cultured
D005938:Glucocorticoids; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D003907:Dexamethasone