| Project/Area Number |
26670551
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Radiation science
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| Research Institution | University of Toyama |
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Principal Investigator |
KONDO Takashi 富山大学, 大学院医学薬学研究部(医学), 教授 (40143937)
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| Co-Investigator(Kenkyū-buntansha) |
SAKURAI Hiroaki 富山大学, 大学院医学薬学研究部(薬学), 教授 (00345571)
ZHAO Qing-Li 富山大学, 大学院医学薬学研究部(医学), 助教 (90313593)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ＴＡＫ１ / 放射線 / 温熱 / 細胞死 / アポトーシス / TAK1 |
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| Outline of Final Research Achievements |
Transforming growth factor-beta-activated kinase1 (TAK1) appears to play an anti-apoptotic role in response to multiple stresses and has been reported to be a responsive kinase that regulates cell survival in KRAS-dependent cells. In this study, we focused on the synergistic effects of 5Z-7-oxozeaenol, a TAK1 inhibitor, with hyperthermia (HT) in KRAS mutant lung cancer cell line A549 cells. Here, enhancement in apoptosis induced by HT exposure was observed, when the cells were pre-incubated with 5Z-7-oxozeaenol. The enhancement was accompanied by significant increase in reactive oxygen species generation and mitochondrial membrane potential loss. In addition, the drug promoted HT-induced expressions of cleaved caspase-3, cleaved caspase-8, HSP70 and decreased HT-induced expressions of Bcl-2, p-p38, p-JNK and LC3. Taken together, our data provides further insights of the mechanism of action of 5Z-7-oxozeaenol and HT treatmentfor patients with KRAS mutant lung cancer.
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