干扰素诱导肿瘤凋亡的分子机制

干扰素(interferons,IFNs)是一类重要的抗病毒、抗肿瘤和免疫调节细胞因子。IFNs广泛用于造血系统恶性肿瘤、淋巴瘤及多种实体瘤的临床治疗。IFNs与细胞表面受体结合后,主要通过JAK/STAT信号途径,调节一系列干扰素刺激基因(IFN-sti mulated genes,ISGs)表达,这些功能性基因包括凋亡相关分子Fas/FasL、TRAIL/APO-2、抑癌基因bax、bak及p53等,这些ISGs与细胞凋亡及抑制细胞周期密切相关。此外,IFN还可放大由caspase诱导的线粒体功能紊乱效应,诱导细胞经线粒体途径凋亡。因而,IFNs主要通过抑制细胞周期、诱导抑癌基因的表达及增强肿瘤细胞对凋亡信号敏感性,诱导肿瘤细胞凋亡,而发挥其抗肿瘤生物学活性。

Molecular mechanisms of interferons-induced apoptosis in tumors

Interferons (IFNs) family members, as important cytokines, exert multiple biological activities including initiating anti-viral and anti-cancer response, immune regulatory function, then they are widely used in the clinical therapy of the malignancies of haemopoietic system, lymphoma and solid tumors. IFN-stimulated genes are modulated mostly through JAK/STAT signaling pathways, including apoptosis-related genes, for example, Fas/FasL, TRAIL/APO-2 etc., and anti-oncogene such as bax, bak and p53 etc., which are correlated with apoptosis and cell cycle inhibition. Moreover, IFNs enlarge the effect of mitochondrial disfunction mediated by caspase and elicit apoptosis through mitochondrial pathway. Thus, IFNs anti-tumor biological activities are presented mostly through inhibiting cell cycle, inducing anti-oncogene expression and mediating apoptosis by sensitizing tumor cells to apoptosis signaling pathway.