Glycogen synthase kinase-3β regulates tumor necrosis factor (TNF)-related apoptosis inducing ligand-

• 作 者: KaiFu[1]HuazhengPan[2]ShihaiLiu[3]JingLv[1]ZhaojunWan[1]JiaoLi[1]QingSun[1]JunLiang[1]
• 机 构: Department of Oncology, the Affiliated Hospital of Qingdao University, Qingdao 266003, P.R.China
• 出 处: 山东省抗癌协会第五次会员代表大会暨山东省第四届肿瘤学术大会
• 发表日期: 2015年期

　　Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known for its ability to selectively induce apoptosis in malignant cells.However, human hepatocellular carcinoma (HCC) cells display resistance to TRAIL-induced cell death.In the present report, we investigated that TRAIL-induced apoptosis in HCC cells were enhanced by the inhibitor of glycogen synthase kinase-3β (GSK-3β) or by shRNA-mediated inhibition of GSK-3β.When investigated for the mechanism, we found that the inhibition of GSK-3β can impair the expression of the NF-κB target genes Bcl-xL and clAP2 in HCC cells.This result suggested that GSK-3β had the potential to regulate NF-κB target genes involved in cell survival.In addition, we observed that knockdown of Bcl-xL enhanced the sensitizing effect of GSK-3β inhibitor on TRAIL-induced apoptosis.Overall, our results provide a rationale for further exploration of GSK-3β inhibitor combined with TRAIL for the treatment of HCC.