Glycogen synthase kinase‑3β regulates tumor necrosis factor‑related apoptosis inducing ligand (TRAIL)‑induced apoptosis via the NF‑κB pathway in hepatocellular carcinoma

Fu,Kai; Pan,Huazheng; Liu,Shihai; Lv,Jing; Wan,Zhaojun; Li,Jiao; Sun,Qing; Liang,Jun

doi:10.3892/ol.2015.3803

Glycogen synthase kinase‑3β regulates tumor necrosis factor‑related apoptosis inducing ligand (TRAIL)‑induced apoptosis via the NF‑κB pathway in hepatocellular carcinoma

Authors:
- Kai Fu
- Huazheng Pan
- Shihai Liu
- Jing Lv
- Zhaojun Wan
- Jiao Li
- Qing Sun
- Jun Liang
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Affiliations: Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Clinical Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China, Central Laboratory, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: October 13, 2015 https://doi.org/10.3892/ol.2015.3803
Pages: 3557-3564

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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.

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