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A recombinant adenoviral vector expressing full-length human retinoblastoma susceptibility gene inhibits human tumor cell growth.
- Source :
-
Cancer gene therapy [Cancer Gene Ther] 1998 Jul-Aug; Vol. 5 (4), pp. 207-14. - Publication Year :
- 1998
-
Abstract
- As a prelude to considering retinoblastoma (RB) gene therapy for cancer, a series of human tumor cell lines with either full-length, mutated, or undetectable RB protein were treated with recombinant adenovirus encoding RB (ACNRB). Both RB protein expression and the cytotoxic and antiproliferative effects of ACNRB treatment were evaluated. While the transgene expression of a reporter virus encoding the beta-galactosidase enzyme (rAd-beta-gal) varied among cell lines, the reintroduction and expression of the RB gene resulted in a pronounced inhibition of cellular proliferation in RB-altered cell lines. An antiproliferative response was observed with control adenovirus treatment in some cell lines. ACNRB treatment did not cause detectable cytotoxicity in either RB+ or RB-altered cells. Dose-dependent cytostasis was observed in RB- cell lines. In vivo tumor suppression was observed in a breast xenograft model subsequent to the treatment of established tumors with ACNRB. These data support a role for RB gene therapy of tumors with RB mutations and provide a basis for the further evaluation of ACNRB gene therapy of human cancer.
- Subjects :
- Animals
Cell Division drug effects
Cell Division genetics
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
G1 Phase drug effects
G1 Phase genetics
Genetic Vectors genetics
Humans
L-Lactate Dehydrogenase drug effects
L-Lactate Dehydrogenase metabolism
Mice
Mice, Nude
Neoplasms, Experimental drug therapy
Neoplasms, Experimental genetics
Recombinant Proteins genetics
Recombinant Proteins metabolism
Recombinant Proteins pharmacology
Retinoblastoma metabolism
Tumor Cells, Cultured drug effects
Adenoviridae genetics
Antineoplastic Agents pharmacology
Genetic Therapy methods
Genetic Vectors pharmacology
Retinoblastoma genetics
Subjects
Details
- Language :
- English
- ISSN :
- 0929-1903
- Volume :
- 5
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cancer gene therapy
- Publication Type :
- Academic Journal
- Accession number :
- 9694072