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

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-3 beta signaling on the anticancer effects of doxorubicin in human CCA cells. Blocking GSK-3 beta 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-3 beta 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-3 beta protects human CCA cells against Dox-induced apoptosis via sustaining FAK/AKT activity.