Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer drug. One obstacle in TRAIL-based therapies is that many cancer cells, including gliomas, are resistant towards TRAIL. In this study one glioblastoma cell line, one human short-term glioblastoma culture and human astrocytes were treated with genistein, tumour necrosis factor-related apoptosis-inducing ligand or the combination of both. Single treatment with genistein or TRAIL does not induce cytotoxicity in malignant glioma cells. However, treatment with genistein in combination with TRAIL induces rapid apoptosis in TRAIL-resistant glioma cells. Notably, normal human astrocytes were not affected by the combination treatment consisting of genistein and TRAIL. Genistein enhanced proteasomal degradation of the short isoform of c-FLIP. Importantly, over-expression of only the short isoform of c-FLIP attenuated genistein TRAIL-mediated cytotoxicity. Taken together, we gave evidence that genistein facilitated TRAIL-mediated apoptosis at the level of the extrinsic apoptotic pathways in malignant glioma cells.

肿瘤生长因子相关凋亡配体（TRAIL）是一种有前景的抗癌药物。许多癌症细胞包括胶质瘤对TRAIL耐受是治疗方面的障碍物。 
本实验中金雀异黄素、肿瘤生长因子相关凋亡配体（TRAIL）或者两者结合使用治疗一种胶质瘤、一种人类短期胶质瘤培养基、人类星型细胞。用金雀异黄素或者肿瘤生长因子相关凋亡配体（TRAIL）单独治疗没有诱发恶性胶质瘤细胞毒性。然而，金雀异黄素与肿瘤生长因子相关凋亡配体（TRAIL）联合治疗可快速诱导TRAIL耐受的胶质瘤细胞的凋亡。 
更令人瞩目的是：两种药物联合治疗对正常的星形细胞没有影响。金雀异黄素强化短c-FLIP亚型 蛋白酶体的降解。重要的是短c-FLIP亚型细胞的过度表达减弱了金雀异黄素对TRAIL-介导细胞毒性的作用。