Nuclear factor-kappaB (
NF kappaB) plays a pivotal role in
cancer progression. In this study, we developed a decoy cis-
element oligo-
deoxyribonucleic acid against
NF kappaB-binding site (
NF kappaB-decoy), which effectively inhibits
NF kappaB activity, and tested the effect of combined
therapy comprising local transfection of
NF kappaB-decoy into the liver and transportal injection of
paclitaxel on
cancer growth and
metastasis using an orthotopic murine model of
colon cancer liver
metastasis. For
NF kappaB-decoy transfection, we employed a novel approach using ultrasound exposure with an echocardiographic
contrast agent,
Optison. We examined the influence of
NF kappaB-decoy transfer on susceptibility to
paclitaxel in
cancer cells and the mechanism involved using several in vitro analysis systems. We then studied the in vivo effect of combined
NF kappaB-decoy transfer and
paclitaxel in preventing
cancer progression using a murine model of liver
metastasis created by splenic injection of a human
colon cancer cell line, HT29. In vitro experiments, including MTT-assay, fluorescence-activated cell sorter and
cDNA array analysis, revealed that
NF kappaB-decoy transfer significantly increased the susceptibility of
cancer cells to
paclitaxel, and that decreased expression of anti-apoptotic genes along with increased expression of genes relevant to the apoptosis-promotor may be involved. In vivo experiments showed that local transfection of
NF kappaB-decoy into the liver followed by portal injection of
paclitaxel effectively induced
cancer cell apoptosis in the liver
metastasis, and significantly prolonged animal survival compared to controls, without notable side effects. In conclusion, a combination of local
NF kappaB-decoy transfer into the liver and transportal injection of
paclitaxel may be a safe and effective new
therapy for liver
metastasis.