|Budget Amount *help
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|Outline of Final Research Achievements
Induction of tumor cell apoptosis is an important for cancer therapy. TNF-related apoptosis inducing ligand (TRAIL) and death receptor 5 (DR5)-mediated apoptosis plays one of the key roles for tumor cell elimination, because this pathway has no effect on normal cells. In TRAIL/DR5-resistant tumor cells, DR5 localizes not only on the cell membrane but also in the nucleus. To translocate of nuclear DR5 to cell membrane, I generated drug-induced knockdown of importin β1 in TRAIL-resistant human tumor cells. These cells and control shRNA cells were xenografted to mice. After the establishment of tumor nodules, drug and anti-DR5 agonistic antibody (Ab) were administrated.
By the drug administration, shRNA was induced in tumor cells. Moreover, in case of drug and anti-DR5 Ab administration, tumor growth was suppressed or tumor nodule was rejected. These data indicated that inhibition of importin β1 may be an useful application of apoptosis induction in tumor cells and cancer therapy.