Antisense oligonucleotide specific for transforming growth factor-beta 1 inhibit both in vitro and in vivo growth of MBT-2 murine bladder cancer.
Anticancer Res
; 18(3A): 1585-9, 1998.
Article
em En
| MEDLINE
| ID: mdl-9673374
ABSTRACT
INTRODUCTION AND OBJECTIVES:
TGF-beta is a potent immunosuppressive cytokine produced by many tumor cells. Secretion of TGF-beta by malignant cells may be a mechanism by which tumor cells escape destruction by tumor-specific T lymphocytes. In this study, we used a TGF-beta producing C3H/He-MBT-2 murine bladder tumor model to investigate the feasibility of antisense oligonucleotide (ODN) gene therapy strategy to block the production of TGF-beta from tumor cells and evaluate its influence on both in vitro tumor growth and in vivo tumor formation. MATERIALS ANDMETHODS:
Using a plasmid, pRUFCD, we constructed a recombinant plasmid pRUFCD/TGF-beta 1(-) containing antisense TGF-beta ODN and then transfected in into MBT-2 cells by electroporation. Three transfectant clones were successfully obtained by their resistance to 5-fluorouracil and cytosine.RESULTS:
The secretion of TGF-beta from the three obtained TGF-beta antisense-blocked MBT-2 cell clones, as assessed by ELISA, were all decreased. Moreover, they all exhibited smaller colony size in the in vitro anchorage-independent soft agar colony forming assay. Tumor growths in mice injected with these three clones were all inhibited compared with those injected with parental tumor cells.CONCLUSION:
This study demonstrates that after reducing the secretion of TGF-beta 1 on tumor cells by TGF-beta 1 antisense, ODN can inhibit their in vitro growth and in vivo tumor formation suggesting that this approach can be a potentially useful strategy to abolish the adverse immunosuppression effect of TGF-beta 1 producing autologous tumor vaccine and therefore to enhance host antitumor immune response.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
/
Oligonucleotídeos Antissenso
/
Fator de Crescimento Transformador beta
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
1998
Tipo de documento:
Article