Neoplasma Vol.52, p.344-351, 2005
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| Title: Tumor targeted gene therapy with plasmid expressing human tumor
necrosis factor alpha in vitro and in vivo
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| Author: A., PASTORAKOVA
; K., HLUBINOVA
; J., BODO
; J., LIBBY
; B., RYCHLY
; G., MARGISON
; C., ALTANER
; |
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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.
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| Keywords: cancer gene therapy, human tumor necrosis factor alpha, apoptosis,
necrosis
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| Year: 2005, Volume: 52, Issue: |
Page From: 344, Page To: 351 |
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