Mechanisms involved in the anti-tumor effect of introduction of a mutant from of I_KBα gene into human oral cancer cells

I_KBα基因突变体导入人口腔癌细胞的抗肿瘤作用机制

• 批准号: 13672102
• 负责人: AZUMA Masayuki
• 金额: $ 2.3万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13672102/
• 关键词: NF-_KB; I_KBα; Head and neck cancers; Apoptosis; Anti-cancer agents; NFкB; lкBα; 血管新生因子

We have demonstrated in this research project as follows:1. Human head and neck cancer cells express an augmented NF-_KB activity as compared to normal cells.2. Inhibition of NF-_KB activity by introduction of a mutant form of I_KBα cDNA results in the suppression of tumor growth of head and neck cancer cells via the inhibition of angiogenesis.3. 5-Fluorouracil induces apoptosis in human salivary gland cancer cells by suppression of NF-_KB via inhibition of I_KB kinase activity.4. Suppression of TNF-α-induced MMP-9 production in human salivary gland acinar cells by Cepharanthine occurs via down-regulation of NF-_KB.5. Cisplatin induces apoptosis in oral squamous carcinoma cells by the mitochondria-mediated but not the NF-_KB-suppressed pathway.

我们在该研究项目中证明了：1。与正常细胞相比，人头和颈部癌细胞表达了增强的NF-_KB活性。2。通过引入I_KBαcDNA突变形式对NF-_KB活性的抑制会导致通过抑制血管生成抑制头颈癌细胞的肿瘤生长。3。 5-氟尿嘧啶通过抑制I_KB激酶活性来抑制NF-_KB。4。通过nf-_kb.5的下调，通过头苯胺抑制人类唾液腺腺苷细胞中TNF-α诱导的MMP-9产生。顺铂诱导线粒体介导的口服鳞状癌细胞中的凋亡，但未诱导NF-_KB抑制的途径。

项目成果

Tetsuya Tamatani: "Enhanced IкB kinase activity is responsible for the augmented activity of NF-кB in human head and neck carcinoma cells."Cancer Lett. 171(2). 165-172 (2001)

Tetsuya Tamatani：“增强的 IкB 激酶活性导致人类头颈癌细胞中 NF-кB 的活性增强。”Cancer Lett 171(2) (2001)。

Keiko Aota: "Stable inhibition of NF-κB in salivary gland cells does not enhance sensitivity to TNF-α-induced apoptosis due to upregulation of TRAF-1 expression"Exp. Cell Res.. 276. 111-119 (2002)

Keiko Aota：“由于 TRAF-1 表达上调，稳定抑制唾液腺细胞中的 NF-κB 不会增强对 TNF-α 诱导的细胞凋亡的敏感性”Exp. 276. 111-119 (2002)

Katsumi Motegi: "Effect of mutant from of I_KB-α on 5-fluorouracil- induced apoptosis in transformed human salivary gland cells."Oral Oncol. 37(2). 185-192 (2001)

Katsumi Motegi：“I_KB-α 突变体对转化人唾液腺细胞中 5-氟尿嘧啶诱导的细胞凋亡的影响。”Oral Oncol 37(2) (2001)。

Katsumi Motegi: "Effect of mutant form of IκB-α on 5-fluorouracil-induced apoptosis in transformed human salivary gland cells"Oral Oncol.. 37. 185-192 (2001)

Katsumi Motegi：“IκB-α 突变形式对转化人唾液腺细胞中 5-氟尿嘧啶诱导的细胞凋亡的影响”Oral Oncol.. 37. 185-192 (2001)

Masayuki Azuma: "Cepharanthine suppresses TNF-α-induced MMP-9 production by downregulating NF-_KB in human salivary gland acinar cells."Arthritis Rheum. 46(6). 1585-1594 (2002)

Masayuki Azuma：“千金藤素通过下调人唾液腺腺泡细胞中的 NF-_KB 来抑制 TNF-α 诱导的 MMP-9 产生。”Arthritis Rheum 46(6) 1585-1594 (2002)。