| Project/Area Number |
22591525
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Digestive surgery
|
|---|
| Research Institution | Kumamoto University |
|---|
Principal Investigator |
ISHIKAWA Shinji 熊本大学, 医学部附属病院, 非常勤診療医師 (80419639)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
BABA Hideo 熊本大学, 大学院・生命科学研究部, 教授 (20240905)
HORINO Kei 熊本大学, 医学部附属病院, 講師 (60452900)
TAKAMORI Hiroshi 熊本大学, 医学部附属病院, 非常勤診療医師 (90363514)
|
|---|
| Project Period (FY) |
2010 – 2012
|
| Project Status |
Completed (Fiscal Year 2012)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | スタチン / EZH2 / p27 / SREBP2 / HDAC5 / 大腸癌 / MC1568 / 消化器癌 / コレステロール合成経路 |
|---|
| Research Abstract |
Although statins led better survival outcomes, the anti-proliferative effects inColorectal cancer (CRC) cells differ in statins (simvastatin >=fluvastatin > atorvastatin> pravastatin). Indeed, the recurrence rate of CRC patients with pravastatin had nodifference compared to patients without statin. As the underlying mechanism, statinsexcept pravastatin showed the anti-cancer effects by inhibiting EZH2-mediated genesilencing of p27KIP1. As a novel epigenetic anti-cancer strategy, a simvastatin plusclassII HDAC inhibitor synergistically induced the anti-proliferative effects byinhibiting EZH2-modulated HDAC5 induction. Thus, as a novel mechanism of statin-inducedanti-cancer effects, EZH2-mediated epigenetic mechanism was identified. Although statinmay lead to survival benefits in CRC patients, its anti-cancer effects differ in statins,suggesting that the kind of statins should be considered in clinical settings.
|
