肿瘤细胞TRAIL耐受与其受体的关系

Relationship between tumor tolerance to TRAIL and its receptors

肿瘤坏死因子相关凋亡诱导配体（TRAIL）能与含有死亡域的死亡受体DR4、DR5相结合，诱导多种肿瘤细胞发生凋亡而对正常细胞无明显毒性。但肿瘤细胞对TRAIL的耐受限制了其广泛应用于临床。受体与配体的结合是凋亡信号启动的起始及关键环节，因此肿瘤细胞发生TRAIL耐受的机制与受体的表达、定位、分布、功能等密切相关。联合其他治疗手段针对受体靶点，实现个体化治疗，有望最终克服肿瘤细胞的TRAIL耐受。

Tumor necrosis factor-related apoptosis-inducing ligand （TRAIL） preferentially induces apoptosis in tumor cells but not in normal cells. It induces apoptosis in its target cells by interacting with surface death receptors DR4 and DR5 ,which contain a cytoplasmic region designated as the ＂ death domain＂. Clinical use of rhTRAIL and its agonistic antibodies is limited due to partial or completetolerance to TRAIL in human tumor cell lines. As TRAIL binding to its death receptors is the initial and crucial step in initiating apoptosis, the mechanisms of TRAIL-tolerance in tumor cells is closely related to the expression, location, distribution and function of TRAIL receptors . Personalized care combined with other therapies targeting TRAIL receptors may be expected to overcome the TRAIL-tolerance of tumor cells eventually.