GSK‑3β inhibition promotes doxorubicin‑induced apoptosis in human cholangiocarcinoma cells via FAK/AKT inhibition

Li,Lei; Xiang,Yuancai; Zeng,Yi; Xiao,Bin; Yu,Wenjing; Duan,Chunyan; Xia,Xianming; Zhang,Ting; Zeng,Yongqiu; Liu,Youping; Dai,Rongyang

doi:10.3892/mmr.2020.11502

GSK‑3β inhibition promotes doxorubicin‑induced apoptosis in human cholangiocarcinoma cells via FAK/AKT inhibition

Authors:
- Lei Li
- Yuancai Xiang
- Yi Zeng
- Bin Xiao
- Wenjing Yu
- Chunyan Duan
- Xianming Xia
- Ting Zhang
- Yongqiu Zeng
- Youping Liu
- Rongyang Dai
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Affiliations: Department of Biochemistry and Molecular Biology, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Hepatobiliary Surgery of the Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China, Department of Medical Cell Biology and Genetics, Southwest Medical University, Luzhou, Sichuan 646000, P.R. China
Published online on: September 10, 2020 https://doi.org/10.3892/mmr.2020.11502
Pages: 4432-4441

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Abstract

Cholangiocarcinoma (CCA) is the most common type of malignant tumor of the bile duct and is characterized by high morbidity and mortality; it is difficult to diagnose in the early stages and responds poorly to current conventional radiotherapy and chemotherapy. The present study investigated the role of GSK‑3β signaling on the anticancer effects of doxorubicin in human CCA cells. Blocking GSK‑3β enhanced the sensitivity of human CCA cells to doxorubicin (Dox)‑induced apoptosis, which was accompanied by decreased AKT and focal adhesion kinase (FAK) activity. Moreover, inhibiting GSK‑3β using 6‑bromoindirubin‑3'‑oxime, CHIR99021 or small interfering RNA decreased phosphorylation of FAK and AKT, and promoted apoptosis of Dox‑induced human CCA cells. Moreover, FAK inhibition suppressed AKT activity independently of phosphoinositide 3‑kinase activity. These results indicated that GSK‑3β protects human CCA cells against Dox‑induced apoptosis via sustaining FAK/AKT activity.

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