Novel molecular therapy targeting aberrant glycogen synthase kinase-3 beta in soft tissue sarcoma

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K20040
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthopaedic surgery
• Research Institution: Kanazawa University
• Principal Investigator: Abe Kensaku 金沢大学, 附属病院, 医員 (60749191)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: GSK-3β / soft tissue sarcoma

Outline of Final Research Achievements

Expression of the active form of GSK3β was higher in sarcoma cells than in fibroblasts. Inhibition of GSK3β activity by pharmacological inhibitors or of its expression by RNA interference suppressed the proliferation of sarcoma cells and induced apoptosis. GSK3β inhibition suppressed the expression of cyclin D1, CDK4 and matrix metalloproteinase (MMP)-2 as well as sarcoma cell invasion of collagen gel. Treatment by intraperitoneal injection of either of the GSK3β inhibitors attenuated the proliferation of sarcoma xenografts in mice in comparison to the mice treated with dimethyl sulfoxide (diluent of GSK3β inhibitor). Pathology examination revealed marked necrosis in the tumors of mice treated with the inhibitor. No obvious side effects or adverse events were observed in the treated mice.

Free Research Field

医歯薬学