Abstract:
:Activation of nuclear factor-κB (NF-κB) has been implicated in metastasis of pancreatic cancer. We investigated the effects of the novel NF-κB inhibitor dehydroxymethylepoxyquinomicin (DHMEQ) on the inhibition of liver metastasis of pancreatic cancer in a mouse model of clinical liver metastasis. Nude mice were xenografted by intra-portal-vein injection with the human pancreatic adenocarcinomas cell line AsPC-1 via small laparotomy. Mice were treated with DHMEQ and gemcitabine (GEM), alone or in combination. The combination of GEM + DHMEQ showed a stronger antitumor effect than either monotherapy. Apoptosis induction in the metastatic foci was greatest in the DHMEQ + GEM group. Significant reductions in the numbers of neovessels were also seen in the DHMEQ and/or GEM groups. Cell growth inhibition assays revealed no synergistic effect of combination therapy, although each monotherapy had an individual cytotoxic effect. Combination therapy produced the greatest inhibition of tumor cell invasiveness in chemoinvasion assay. In addition, combination therapy significantly down-regulated the expression level of matrix metalloproteinase (MMP)-9 mRNA in AsPC-1 cells. DHMEQ also markedly down-regulated interleukin-8 and MMP-9, while GEM caused moderate down-regulation of vascular endothelial growth factor in metastatic foci, demonstrated by quantitative reverse transcription-polymerase chain reaction. These results demonstrate that DHMEQ can exert anti-tumor effects by inhibiting angiogenesis and tumor cell invasion, and by inducing apoptosis. Combination therapy with DHMEQ and GEM also showed potential efficacy. DHMEQ is a promising drug for the treatment of advanced pancreatic cancer.
journal_name
Clin Exp Metastasisjournal_title
Clinical & experimental metastasisauthors
Suzuki K,Aiura K,Matsuda S,Itano O,Takeuchi O,Umezawa K,Kitagawa Ydoi
10.1007/s10585-012-9544-7subject
Has Abstractpub_date
2013-04-01 00:00:00pages
381-92issue
4eissn
0262-0898issn
1573-7276journal_volume
30pub_type
杂志文章abstract::Emerging data in myeloma and other cancers indicates that heparan sulfate proteoglycans promote tumor progression by enhancing their growth and metastasis. By acting as key regulators of cell signaling via their interactions with multiple growth and angiogenic factors, heparan sulfates mediate a shift in the microenvi...
journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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更新日期:1994-07-01 00:00:00
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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更新日期:2011-12-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1007/s10585-006-9007-0
更新日期:2005-01-01 00:00:00
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
doi:10.1023/a:1006568103588
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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更新日期:2017-02-01 00:00:00
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
pub_type: 杂志文章,评审
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journal_title:Clinical & experimental metastasis
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journal_title:Clinical & experimental metastasis
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