Yang Lijun, Wang Yutao, Zheng Haifeng, Zhang Dong, Wu Xiangwei, Sun Gongqin, Yang Tao
a Department of Biochemistry and Molecular Biology , Shanxi Medical University , Taiyuan , China.
b Department of Clinical Cancer Prevention , The University of Texas MD Anderson Cancer Center , Houston , TX , USA.
J Chemother. 2017 Jun;29(3):179-188. doi: 10.1080/1120009X.2016.1277048. Epub 2017 Jan 9.
Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer treatment due to its highly selective apoptosis-inducing action on tumour cells without harming normal cells. However, because of TRAIL resistance by some cancer cells, combined treatment with sensitizing agents is required to enhance the anticancer potential of TRAIL. In the present study, we investigated the sensitizing effect of 5-fluorouracil (5-FU) on TRAIL-induced apoptosis in TRAIL-resistant HepG2 hepatocarcinoma cells. The results show that 5-FU pretreatment could sensitize HepG2 cells to TRAIL-mediated apoptosis. The enhanced induction of cell death by the 5-FU/TRAIL combination was mediated by DR5 up-regulation and survivin down-regulation. Furthermore, this combination treatment significantly inhibited the growth of human xenografts in vivo. In conclusion, this study demonstrates that the combination of a sensitizing agent and TRAIL may be a novel and effective therapeutic regimen for treating human hepatocellular carcinoma.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）因其对肿瘤细胞具有高度选择性的凋亡诱导作用且不损害正常细胞，是一种很有前景的癌症治疗候选药物。然而，由于一些癌细胞对TRAIL耐药，需要与增敏剂联合治疗以增强TRAIL的抗癌潜力。在本研究中，我们研究了5-氟尿嘧啶（5-FU）对TRAIL耐药的HepG2肝癌细胞中TRAIL诱导凋亡的增敏作用。结果表明，5-FU预处理可使HepG2细胞对TRAIL介导的凋亡敏感。5-FU/TRAIL联合用药增强的细胞死亡诱导作用是由DR5上调和生存素下调介导的。此外，这种联合治疗在体内显著抑制了人异种移植瘤的生长。总之，本研究表明增敏剂与TRAIL联合可能是治疗人类肝细胞癌的一种新型有效治疗方案。
