Tumor targeted gene therapy with plasmid expressing human tumor necrosis factor alpha in vitro and in vivo.
Pastorakova, A Hlubinova, K Bodo, J Libby, J Rychly, B Margison, Geoffrey P Altaner, C
Pastorakova, A
Hlubinova, K
Bodo, J
Libby, J
Rychly, B
Margison, Geoffrey P
Altaner, C
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Abstract
We have assessed the effect of exogenous human tumor necrosis factor alpha (hTNFalpha) in three human cancer cell lines; MDA-MB-361 (breast adenocarcinoma), HCT 116 (colon carcinoma) and 8-MG-BA (glioma). In vitro transfection of a plasmid containing hTNFalpha under the control of a hybrid promoter resulted in expression of hTNFalpha gene in all three cell lines and secretion into the culture medium was seen with MDA-MB-361 cells. Flow cytometric analysis showed a significant increase in apoptotic and necrotic cells in MDA-MB-361 and to a lesser extent in HCT 116 cells. Increased apoptosis was confirmed by an increase in pro-caspase 3 activation. No effects of hTNFalpha expression were seen in 8-MG-BA cells. Intratumoral delivery of the hTNFalpha expression plasmid into MDA-MB-361 tumor xenografts grown in nude mice caused hemorrhagic tumor necrosis. This strategy may be a simple and promising gene therapy approach to the treatment of some human tumors.
Description
Date
2005
Publisher
Collections
Keywords
Brain Cancer
Breast Cancer
Colonic Cancer
Tumour Cells
Tumour Necrosis
Breast Cancer
Colonic Cancer
Tumour Cells
Tumour Necrosis
Type
Article
Citation
Tumor targeted gene therapy with plasmid expressing human tumor necrosis factor alpha in vitro and in vivo. 2005, 52 (4):344-51 Neoplasma