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

我们研究了抗癌药物（CDDP、5-Fu）、IFN-γ或NO供体（SNP、SNAP、NOC）对主要在从舌鳞状细胞癌建立的NA细胞中诱导凋亡的影响。进一步研究这些药物对NA细胞中c-myc和c-myb表达、粘附分子ICAM-1、Fas/Fas配体和可溶性Fas的影响。主要研究结果如下：1. NO供体诱导NA细胞凋亡，同时抑制c-myc和c-myb mRNA的表达. CDDP和5-Eu可诱导NA细胞凋亡，提示FLICE（caspase 8）可能参与了诱导NA细胞凋亡的过程。然而，当NA细胞与这些抗癌药物一起处理时，没有观察到协同效应。CDDP和5- Eu均能促进NA细胞ICAM-1的表达，CDDP和5-Eu联合作用对ICAM-1的诱导有协同作用。当用IEN-γ或抗Fas抗体（CH 11）处理NA细胞时，诱导凋亡。细胞膜结合Fas无明显变化，而细胞培养液中可溶性Eas减少.用IFN-γ或TNF-α处理HL-60细胞后，HL-60细胞表面Fas和Fas配体的表达增强，bcl-2蛋白及其mRNA的表达降低，表明抗肿瘤药物或NO供体均可诱导细胞凋亡，IFN-γ或TNF-α可增强细胞凋亡的诱导作用。

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.