Gankyrin promotes the proliferation of gastric cancer and is associated with chemosensitivity.

Abstract

Although gankyrin is involved in the tumorigenicity and metastasis of some malignancies, the role of gankyrin in gastric cancer is not clear. In this study, we evaluated the function and mechanism of gankyrin in gastric cancer. The effects of gankyrin on gastric cancer growth, proliferation, and chemosensitivity were determined. Gankyrin expression was significantly increased in gastric cancer compared to non-cancerous tissues. This expression significantly enhanced cancer cell proliferation and growth in vitro and in vivo. Suppression of gankyrin downregulated cyclin D1, cyclin E, proliferating cell nuclear antigen, phosphoinositide 3-kinase, AKT, p-PI3K, and p-AKT but upregulated Rb, p53, and p27. However, gankyrin overexpression led to opposite results. Downregulation of gankyrin expression enhanced chemosensitivity to 5-fluorouracil and cisplatin by inducing cell apoptosis. However, upregulation of gankyrin expression led to the opposite outcomes. Gankyrin enhanced gastric cancer cell proliferation by regulating cell cycle-related proteins and by activating PI3K/AKT signaling pathway. Gankyrin played an important role in gastric carcinogenesis and could be a potential effective therapeutic target for enhancing chemosensitivity to 5-fluorouracil and cisplatin.