Project/Area Number |
15K09165
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
|
Research Institution | Asahikawa Medical College |
Principal Investigator |
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
Keywords | KRAS / NSCLC / Nampt / 肺癌 |
Outline of Final Research Achievements |
The aim of our study is to evaluate efficacy of nampt inhibitor in KRAS mutated non-small cell lung cancer (NSCLC) and to study the mechanisms. We found that KRAS mutated NSCLC cell lines were divided into three groups; cell lines sensitive to FK866, a nampt inhibitor; those resistant to the inhibitor; intermediate sensitivity. Our study revealed that FK866 inhibited phosphorylation of Rb at ser 807/811, suppressed MAPK signaling pathways, decreased phosphorylation of Bim at ser 69, and increased γH2AX levels. These findings suggest that the nampt inhibitor causes DNA damage, suppresses cell cycle through alteration of Rb and MAPK pathways, and induces apoptosis through stabilization of Bim.
|