干扰素对肿瘤细胞Fas表达的上调作用及与细胞凋亡的关系

Interferon-γ up-regulates Fas expression and increases Fas-mediated apoptosis in tumor cell lines

目的研究干扰素(IFN)对肿瘤细胞表面Fas表达的调控,探讨其致凋亡机制。方法通过流式细胞仪测定肿瘤细胞的Fas表达,应用ELISA及Annexin V 染色检测细胞凋亡。对干扰素及抗Fas单克隆抗体诱导的肿瘤细胞凋亡进行评价。结果胃癌细胞系Kato-Ⅲ、AGS、肺癌细胞A549及喉癌细胞Hep-2均有不同程度的Fas表达,上述细胞与IFN-酌作用后Fas表达升高(P<0.05);IFN- 酌单独即可引起肿瘤细胞凋亡,同时可增加肿瘤细胞对抗Fas抗体的敏感性;IFN- 酌致凋亡及调节Fas表达的作用有时间依赖性,但不同细胞系对这两种因素致凋亡的敏感性不同。结论IFN治疗肿瘤的作用机制之一是增加肿瘤细胞Fas表达而致其凋亡,表明该药在肿瘤生物治疗中应用的合理性。

Objective To investigate effect of interferon-γ (IFN-γ) on Fas expression and Fas-mediated apoptosis in tumor cell lines. Methods Fas expression was detected by flow cytometry, and the tumor cell apoptosis evaluated by enzyme-linked immunosorbent assay and AnnexinV staining assay. Results All the 4 tumor cell lines used in this study, e.g. gastric cancer cell lines Kato-Ⅲand AGS, lung cancer cell line A549 and laryngeal cancer cell line Hep-2, expressed Fas protein to varied degrees. Fas expression was up-regulated by IFN-γ (P<0.05), which alone was enough to induce apoptosis in tumor cells and increase the susceptibility of them to anti-Fas antibodies. IFN-γ induced Fas expression up-regulation and tumor cell apoptosis in a time-dependent manner. Conclusion Fas-mediated apoptosis is one of the mechanisms for IFN-γ to exercise its anti-tumor effect.