title: Glycogen synthase kinase-3β regulates tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis via the NF-κB pathway in hepatocellular carcinoma.
abstract: 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. The present study investigated whether TRAIL-induced apoptosis in HCC cells was enhanced by the administration of an inhibitor of glycogen synthase kinase-3β (GSK-3β) or by short hairpin RNA-mediated inhibition of GSK-3β. The results of the current study demonstrated that inhibition of GSK-3β significantly impairs the expression of the nuclear factor-κB (NF-κB) target genes Bcl-xL and clAP2 in HCC cells (P<0.05). This indicates that GSK-3β may regulate NF-κB target genes involved in cell survival. Furthermore, knockdown of Bcl-xL significantly enhanced the sensitizing effect of GSK-3β inhibitor on TRAIL-induced apoptosis (P<0.05). Overall, the present study provides a rationale for further exploration of GSK-3β inhibition combined with TRAIL as a novel treatment for HCC.
authors.affiliation: Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Kai
authors.initials: K
authors.lastname: Fu
authors.affiliation: Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Huazheng
authors.initials: H
authors.lastname: Pan
authors.affiliation: Central Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Shihai
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Wan
authors.affiliation: Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.affiliation: Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
keywords: apoptosis; glycogen synthase kinase-3β; hepatocellular carcinoma; nuclear factor-κB; tumor necrosis factor-related apoptosis-inducing ligand