Possibility of new treatment modality by inhibition of anti-apoptotic molecule XIAP

通过抑制抗凋亡分子 XIAP 的新治疗方式的可能性

• 批准号: 14370506
• 负责人: TOMITA Yoshihiko
• 金额: $ 8万
• 依托单位: Yamagata University Faculty of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370506/
• 关键词: Urological cancer; apoptosis; renal cell cancer; XIAP; FAs; urinary bladder cancer; Bcl-2; 尿路上皮癌; カスペース; 遺伝子治療

Detailed study of inter-molecular mechanism in apoptotic machinery of tumor cells may contribute to invention of new modality of cancer therapy. In the present study, a putative anti-apoptotic molecule, XIAP, was investigated in terms its expression and action for new modality of treatment. < design and examination of its action of short interference (si) RNA to XIAP> Previous study revealed insufficient inhibition of XIAP tempted us to use siRNA instead. Three sequences were used to siRNA and cloned into a plasmid vector good for siRNA. One of the three siRNA was most potent to knock down XIAP expression. <stable transfectant> Ten to twelve clones each were isolated from transfection of the vector to Caki-1 or LNCap, and under investigation of its function. <XIAP expression and its relation to CRP, interleukin (IL)-6 and tumor necrosis factor(TNF) pathway> Statistically significant correlation between XIAP expression and serum CRP was noticed in renal cell cancer patients. Among cultured cell lines, some of them secreted high titer of IL-6 and TNF-alpha, and frequently expressed XIAP. This indicates that possibility of double inhibition of XIAP expression itself and TNF pathway render more complete inhibition of XIAP leading to more susceptible to apoptotic stimuli. Further examination was being performed.

对肿瘤细胞凋亡机制中分子间机制的详细研究可能有助于发明新的癌症治疗方式。在本研究中，对推定的抗凋亡分子XIAP进行了研究，该分子的表达和作用是新的治疗方式。 <设计和检查其短干扰（SI）RNA对XIAP>先前的研究表明，对XIAP的抑制不足使我们改为使用siRNA。三个序列用于siRNA，并将其克隆到适合siRNA的质粒载体中。三个siRNA之一最有效地击倒XIAP表达。 <稳定的转染剂> 10至十二个克隆从向载体转染至Caki-1或LNCAP的转染中分离出来，并在其功能的研究中分离出来。 <XIAP的表达及其与CRP，白介素（IL）-6和肿瘤坏死因子（TNF）途径的关系>在肾细胞癌患者中注意到了XIAP表达与血清CRP之间的统计学意义相关性。在培养的细胞系中，其中一些是IL-6和TNF-Alpha的高滴度，并且经常表达为XIAP。这表明双重抑制XIAP表达本身和TNF途径的可能性使对XIAP的抑制更加完整，从而更容易受到凋亡刺激的影响。正在进行进一步检查。

项目成果

The role of IRF-1 and caspase-7 in IFN-gamma enhancement of Fas-mediated apoptosis in ACHN renal cell carcinoma cells.

IRF-1 和 caspase-7 在 IFN-γ 增强 ACHN 肾细胞癌细胞 Fas 介导的细胞凋亡中的作用。

• 发表时间: 2003
• 期刊: Int.J.Cancer 104
• 作者: Kihara K;Kageyama Y;Yano M;Kobayashi T;Kawakami S;Fujii Y;Masuda H;Hyochi N;Y.Tomita et al.
• 通讯作者: Y.Tomita et al.

Bilim V, 他: "Role of XIAP in the malignant phenotype,【triple bond】"International Journal of Cancer. 103巻1号. 29-37 (2003)

Bilim V 等人：“XIAP 在恶性表型中的作用，[三键]”《国际癌症杂志》第 103 卷，第 1. 29-37 期（2003 年）。