2015 Fiscal Year Final Research Report
The impact of JNK activity on the cancer stem cells
| Project/Area Number |
26830065
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | Yamagata University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Keywords | がん幹細胞 / 腫瘍発生 / JNK / ROS / 薬剤抵抗性 / Kras |
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| Outline of Final Research Achievements |
In this study, we demonstrated that JNK activity is necessary for maintenance of cancer stem cell (CSC) capacity on pancreatic CSCs as well as glioblastoma and lung CSCs in our previous reports. SP600125, a JNK inhibitor, treatment inhibits self-renewal and tumor-initiating capacity. Moreover, systemic administration of SP600125 reduces tumor-initiating CSCs in vivo. The SP600125 has been used in the overwhelming majority of studies, but the clinical safety profile is unknown. Therefore, we used a novel JNK inhibitor, AS602801 that has been developed for the treatment of inflammatory endometriosis. The AS602801 treatment also inhibits CSC capacity and tumor initiating capacity in vitro and in vivo. Generally chemoresistance associated with CSCs, we show that JNK is critically involved in the resistance of pancreatic CSCs to 5-FU and gemcitabine. The JNK inhibition promotes 5-FU or GEM-induced increase of intracellular reactive oxygen species.
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| Free Research Field |
腫瘍生物学
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