XAF1增加TRAIL诱导的肝癌细胞凋亡的敏感性

XAF1 Increases the Sensitivity of TRAIL-induced Apoptosis in Hepatocellular Carcinoma Cells

背景：肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）可特异性诱导肿瘤细胞凋亡，但部分肿瘤细胞对TRAIL不敏感甚至耐药。目的：探讨X连锁凋亡抑制蛋白（XIAP）相关因子1（XAF1）是否可增加TRAIL诱导的肝癌细胞株凋亡的敏感性。方法：重组人TRAIL（rhTRAIL）因子分别加入3株肝癌细胞株SMMC7721、HepG2和Bel-7404中培养，联合或不联合相同感染复数（MOI）的重组腺病毒Ad5／F35-XAF1和对照空病毒Ad5／F35-Null。作用48h后，以MTT检测细胞活力，以AnnexinV—FITC／PI法检测细胞凋亡率。结果：随着TRAIL浓度的增加，3株肝癌细胞株的细胞活力均不同程度降低。TRAIL与Ad5／F35-XAFI联合作用后，其细胞活力显著低于单独TRAIL组，而Ad5／F35-Null组细胞活力与单独TRAIL组无明显差异。与空白对照组和Ad5／F35-Null组相比．TRAIL组和Ad5／F35-XAF1组3株肝癌细胞株的凋亡率均显著增加。TRAIL与Ad5／F35-XAF1联合作用后．细胞凋亡率显著高于Ad5／F35-XAF1组或TRAIL组。结论：XAF1可明显增加TRAIL诱导的肝癌细胞凋亡的敏感性．两者联合应用对诱导不同肝癌细胞凋亡具有协同作用。

Background： Tumor necrosis factor （TNF）-related apoptosis-inducing ligand （TRAIL） can specifically induce apoptosis of tumor cells, but a portion of tumor cells are less sensitive or even resistant to TRAIL. Aims： To investigate the effect of X-linked inhibitor of apoptosis protein （XIAP）-associated factor 1 （XAF1） on sensitizing TRAIL-induced apoptosis of hepatocellular carcinoma cell lines. Methods： Recombinant human TRAIL （rhTRAIL） was co-cultured with 3 hepatocellular carcinoma cell lines SMMC7721, HepG2 and Bel-7404, with or without the addition of recombinant adenovirus AdS/F35-XAF1 or control empty virus AdS/F35-Null at the same multiplicity of infection （MOI）. MTT assay was used to evaluate cell viability. Cell apoptosis was determined by Annexin V-FITC/PI. Results： With the increasing concentration of TRAIL, cell viability of 3 hepatoeellular carcinoma cell lines was decreased in all groups. Compared with TRAIL group, cell viability of 3 hepatocellular carcinoma cell lines was significantly decreased when TRAIL was combined with AdS/F35-XAF1, but no significant differeuce was found between TRAIL group and TRAIL combined with AdS/F35-Null group. The apoptosis rates of 3 hepatocellular carcinoma cell lines were significantly increased in TRAIL group and AdS/F35-XAF1 group than those in control empty group and AdS/F35-Null group. Compared with AdS/F35- XAF1 group or TRAIL group, cell apoptosis was rapidly enhanced when TRAIL combined with AdS/F35-XAF1. Conclusions： XAF1 may increase the sensitivity of TRAIL-induced cell apoptosis. Combined use of XAF1 and TRAIL may have synergistic effect on inducing the apoptosis of hepatocellular carcinoma cells.