Abstract:
BACKGROUND:Nuclear factor-kappaB (NF-kappaB) is synthesized in the cytoplasm, complexed with its inhibitor, I-kappaB, and NF-kappaB is released in an activated (phosphorylated) form following phosphorylation of I-kappaB and proteasomal degradation of the NF-kappaB.p-kappaB complex. The free p-NF-kappaB can then be translocated to the nucleus where it effects transcriptional activation of genes leading to the synthesis of proteins that are generally pro-growth and anti-apoptosis. OBJECTIVE:To gain insight into the role of the NF-kappaB pathway in head and neck squamous cell carcinoma (HNSCC), we selected two HNSCC cell lines, SCC-15 of lingual origin and FaDu of pharyngeal origin, with constitutively activated (phosphorylated) NF-kappaB. We assessed the impact of interrupting the NF-kappaB pathway at the level of proteasomal degradation using Velcade (bortezomib), a proteasome inhibitor, and at the pretranslational level in the synthesis of NF-kappaB using a small interfering RNA (siRNA). RESULTS:Velcade produced a dose-dependent inhibition of cell growth in both cell lines. At 30 nM, Velcade inhibited cell growth in the SCC-15 cell line by 40%. In both cell lines, Velcade induced nuclear overexpression of p21(WAF1), an inhibitor of G1 cell cycle progression, which appeared to be independent of p53 expression. Addition of siRNA augmented the inhibitory effects of Velcade in FaDu cells; siRNA/NF-kappaB alone led to a 48% decline in basal expression of NF-kappaB protein levels and effected a 25% inhibition of cell growth. In the presence of Velcade (30 nM), siRNA/NF-kappaB increased growth inhibition from 43 to 65%. CONCLUSIONS:The mechanisms involved in growth inhibitory effects of Velcade on HNSCC cell lines include the NF-kappaB pathway, suggesting the possible therapeutic use of Velcade or other NF-kappaB pathway inhibitors (eg, curcumin). The data also suggest that combining siRNA/NF-kappaB with Velcade might achieve greater reduction in the growth of HNSCC in patients with constitutively activated NF-kappaB.
journal_name
Ann Clin Lab Scijournal_title
Annals of clinical and laboratory scienceauthors
Lun M,Zhang PL,Pellitteri PK,Law A,Kennedy TL,Brown REsubject
Has Abstractpub_date
2005-07-01 00:00:00pages
251-8issue
3eissn
0091-7370issn
1550-8080pii
35/3/251journal_volume
35pub_type
杂志文章abstract::Degenerative joint disease (DJD) is characterized by pain on use. X-rays show cartilage narrowing and osteophytes. Synovial effusions are non-inflammatory, i.e. clear wiht good viscosity and less than 2000 WBC per mm. 3 Cartilage fragments may be seen in the joint fluid. Important systemic diseases that can cause dege...
journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
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abstract::Lead poisoning is an ancient and modern problem. Since many artists have had exposure to lead, it is appropriate to use some of their works as a vehicle to depict the symptoms of the variable syndromes associated with lead exposure. ...
journal_title:Annals of clinical and laboratory science
pub_type: 历史文章,杂志文章
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abstract::The T-cell immunoglobulin and mucin domain containing molecule 3 (TIM-3) gene is an important immune regulatory molecule. In fact, studies have shown that polymorphisms in the (TIM-3) gene may be associated with various cancers. The goal of this study was to investigate whether the -1516G/T, -574G/T, or +4259T/G singl...
journal_title:Annals of clinical and laboratory science
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
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journal_title:Annals of clinical and laboratory science
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pub_type: 杂志文章
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journal_title:Annals of clinical and laboratory science
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journal_title:Annals of clinical and laboratory science
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journal_title:Annals of clinical and laboratory science
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
doi:
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
doi:
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
doi:
更新日期:1978-05-01 00:00:00
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章,评审
doi:
更新日期:2016-01-01 00:00:00
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journal_title:Annals of clinical and laboratory science
pub_type: 临床试验,杂志文章
doi:
更新日期:2011-04-01 00:00:00
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
doi:
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
doi:
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
doi:
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
doi:
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journal_title:Annals of clinical and laboratory science
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doi:
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
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journal_title:Annals of clinical and laboratory science
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journal_title:Annals of clinical and laboratory science
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章,评审
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journal_title:Annals of clinical and laboratory science
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journal_title:Annals of clinical and laboratory science
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journal_title:Annals of clinical and laboratory science
pub_type: 杂志文章
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journal_title:Annals of clinical and laboratory science
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