chir-99021 and Cholangiocarcinoma

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.

Topics: Bile Duct Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cholangiocarcinoma; Doxorubicin; Drug Resistance, Neoplasm; Drug Synergism; Focal Adhesion Kinase 1; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3 beta; Humans; Indoles; Oximes; Phosphorylation; Proto-Oncogene Proteins c-akt; Pyridines; Pyrimidines; RNA, Small Interfering