A new cancer therapy by intracellular localization control of apoptosis inducing death receptor in tumor cells

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590092
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Juntendo University
• Principal Investigator: KOJIMA Yuko 順天堂大学, 医学(系)研究科(研究院), 助教 (60231312)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 腫瘍細胞 / アポトーシス / 分子局在 / がん治療 / インポーチン / TRAIL / Death receptor 5

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.

Free Research Field

生物系薬学