| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
Endo-lysosomal activity was enhanced in the colorectal cancer stem cell (CSC) population, and sphere formation ability from single cells, tumorigenicity and anticancer drug resistance were highly retained. Chemical screening was performed to identify mefloquine as a endo-lysosome maturation inhibitor. Treatment of colorectal cancer cells with mefloquine efficiently eliminated CSC population. Mefloquine showed an synergistic antitumor effect with oxaliplatin and irinotecan, and that the tumor engrafted in mice almost completely disappeared by mefloquine treatment. Microarray analysis and protein binding analysis showed that mefloquine targets the lysosomal pathway regulator, RAB 5/7. Pathway analysis showed that mefloquine impair the mitochondrial metabolism and induce mitochondria induced cell apoptosis.
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