| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| 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.
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