Eradication of radioresistant cancer stem cells by inhibiting the AKT survival signaling pathway.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24510063
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: National Institute of Public Health
• Principal Investigator: SHIMURA Tsutomu 国立保健医療科学院, その他部局等, その他 (40463799)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 放射線 / がん

Outline of Final Research Achievements

Radioresistance, which is a major cause of failure of radiotherapy (RT), is proposed as one of the intrinsic characteristics of cancer stem cells (CSCs) whose unique DNA damage response (DDR), efficient DNA repair and resistance to apoptosis are thought to confer the phenotype. We have isolated surviving CSCs by exposure to long-term fractionated radiation for 82 days from HepG2 cells (82FR-31NR cells). 82FR-31NR cells exhibited CSC properties, such as high expression of CSC marker CD133 and the ABC transporters (MDR1 and BCRP1), and high tumorigenic potential after transplantation into nude mice. 82FR-31NR cells showed efficient DNA repair of radiation-induced DNA damage and radioresistance with activation of the AKT signaling pathway. Therefore, inhibition of the AKT　pathway by an AKT inhibitor, resulted in radiosensitization of 82FR-31NR cells. Combination of fractionated RT and reagents targeting the AKT　pathway to eradicate CSCs would be effective therapeutic modality.

Free Research Field

放射線生物学