Basic research for oral cancer therapy by anti-cancer drugs and apoptosis-inducing factor

抗癌药物和凋亡诱导因子治疗口腔癌的基础研究

基本信息

批准号：
09557171
负责人：
NAGUMO Masao
金额：
$ 7.04万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557171/
关键词：
CDDP 5-Fu NO donors apoptosis ICAM-1 caspase Fas Fas L TNF-alpha 5-FU FasL SNP 可溶性Fas IFN-γ

项目摘要

We investigated the effects of anti-cancer drugs (CDDP, 5-Fu) , IFN-y or NO donors(SNP, SNAP, NOC) on induction of apoptosis mainly in NA cells which had been established from a squamous cell carcinoma of the tongue. Further the effects of these agents on the expression of c-myc and c-myb, adhesion molecules including ICAM-1, Fas/Fas ligand, and soluble Fas were also studied in NA cells. The results obtained were as follows :1. When NA cells were treated with NO donors, apoptosis of NA cells was induced together with the inhibition of the expression of c-myc and c-myb mRNA.2. CDDP and 5-Eu induced apoptosis of NA cells and it was suggested that FLICE (caspase 8) might be concerned in the induction of apoptosis of NA cells. However, synergistic -effect was not observed when NA cells were treated both with these anti-cancer drugs.3. ICAM-1 expression on NA cells was enhanced by the treatment of CDDP or 5- Eu, and simultaneous treatment with CDDP and 5-Eu exhibited synergistic effect on the induction of ICAM-1.4. Apoptosis was induced when NA cells were treated with IEN-gamma or anti-Fas antibody (CH11). Then, membrane binding Fas was not altered, whereas soluble Eas in the medium was decreased.5. The expression of Fas and Fas ligand on HL-60 cells, a leukemia cell line, was enhanced by the treatment with IEN-gamma or TNF-alpha, while the expression of bcl-2 protein and its mRNA was reduced by the treatment.These results indicate that apoptosis is induced both by anti-cancer drugs or NO donors and that the induction of apoptosis is enhanced by IFN-gamma or TNF-alpha.

我们研究了抗癌药物（CDDP、5-Fu）、IFN-y 或 NO 供体（SNP、SNAP、NOC）对主要在从舌鳞状细胞癌建立的 NA 细胞中诱导细胞凋亡的影响。此外，还在 NA 细胞中研究了这些药物对 c-myc 和 c-myb、粘附分子（包括 ICAM-1、Fas/Fas 配体和可溶性 Fas）表达的影响。得到的结果如下： 1． NO供体处理NA细胞后，可诱导NA细胞凋亡，同时抑制c-myc和c-myb mRNA的表达。2． CDDP和5-Eu诱导NA细胞凋亡，提示FLICE（caspase 8）可能参与诱导NA细胞凋亡。然而，当NA细胞同时用这些抗癌药物处理时，没有观察到协同效应。3． CDDP或5-Eu处理可增强NA细胞上ICAM-1的表达，CDDP和5-Eu同时处理对ICAM-1.4的诱导表现出协同作用。当 NA 细胞用 IEN-gamma 或抗 Fas 抗体 (CH11) 处理时，会诱导细胞凋亡。然后，膜结合Fas没有改变，而培养基中可溶性Eas减少。5． IEN-γ或TNF-α处理后，白血病细胞系HL-60细胞上Fas和Fas配体的表达增强，而bcl-2蛋白及其mRNA的表达降低。结果表明，抗癌药物或NO供体均可诱导细胞凋亡，并且IFN-γ或TNF-α可增强细胞凋亡的诱导。