抗Fas mAb和IFN联合诱导胃癌细胞凋亡的实验研究

Effect of combined anti-Fas mAb and IFN-γ on the induction of apoptosis in human gastric carcinoma cell line SGC-7901

目的观察联合应用抗 Fas 单克隆抗体(mAb)和干扰素-γ(IFNγ)诱导人胃癌细胞系 SGC-7901细胞凋亡,并探讨其在胃癌治疗中的意义.方法应用细胞形态观察、琼脂糖凝胶电泳、流式细胞光度术检测抗 Fas mAb,IFN-γ单独及联合应用诱导的人胃癌细胞系SGC-7901细胞凋亡,并应用流式细胞光度术检测 IFN-γ对人胃癌细胞系 SGC-7901细胞表达 Fas 抗原的影响.结果抗 Fas mAb 显著诱导 SGC-7901细胞凋亡(19.3%),细胞 DNA 裂解片段呈现典型的"阶梯状"排列的条带.联合应用抗 Fas mAb 和 IFN-γ处理人胃癌细胞系 SGC-7901细胞凋亡率(29.4%)显著高于对照组、IFN-γ及抗 Fas mAb 处理组(1.2%,1.9%,19.3%,t=17.345,17.276,5.425,P<0.01及P<0.05).IFN-γ处理组人胃癌细胞系 SGC-7901细胞 Fas 抗原的表达阳性细胞数(59.3%)显著高于对照组(27.1%,t=12.995,P<0.05),抗 Fas mAb 诱导 SGC-7901细胞凋亡的敏感性与 Fas 抗原的表达水平显著相关.结论抗 Fas mAb 可以诱导 SGC-7901细胞凋亡.联合应用抗Fas mAb 和 IFN-γ具有协同诱导人胃癌细胞凋亡的作用,其机制可能与干扰素-γ显著上调人胃癌细胞系 SGC-7901细胞Fas 抗原的表达水平有关.

AIM To investigate the effect of combined anti-Fas mAb and IFN-γ on the induction of apoptosis in human gastric carcinoma cell line SGC-7901,and analyze its role in treatment of gastric carcinoma. METHODS Anti-Fas mAb and IFN-γ was tested for their effect on cell injury in gastric carcinoma cell line SGC-7901 with cell morphology,agarose gel electrophoresis and flow cytomety.Fas antigen expression in SGC-7901 cells was also examined. RESULTS Anti-Fas mAb could trigger tumor cell death by inducing apoptosis(19.3%),internucleosomal DNA fragmentation displayed the characteristic ladder-like arrangement of the electrophoretic bands.When the tumor cells were treated with combined anti-Fas mAb and IFN-γ,the apoptosis cells(29.4%)were significantly increased as against control group,IFN-γ group and anti- FasmAbgroup(1.2%,1.9%,19.3%,t=17.345,17.276, 5.425,P<0.01 and P<0.05).IFN-γ could significantly upregulate Fas antigen expression in SGC-7901 cells (59.3% vs 27.1%,t=12.995,P<0.05).The susceptibility of induction apoptosis to anti-Fas mAb was correlated well with the expression level of Fas antigen. CONCLUSION Anti-Fas mAb could induce human gastric carcinoma cell line SGC-7901 apoptosis.Anti-Fas mAb and IFN-γ could synergistically induce apoptosis of SGC-7901 tumor cells,one of the mechanisms may be that IFN-γ could significantly upregulate Fas antigen expression in SGC-7901 cells.