| Project/Area Number |
24790694
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肝癌 / 細胞死 |
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| Research Abstract |
In this project, we aimed to clarify the impact of chemotherapy on innate immune system and cell death signaling in liver cancer, which may provide insights to improve the therapeutic outcome. First, we studied the effect of 5-FU in mice with metastatic liver cancer. 5-FU treatment resulted in an upregulation of NKG2D activating molecules. Depletion of NK cells inhibited the antitumor efficacy of 5-FU. Combination therapy of aGalCer and 5-FU showed a synergistic antitumor effect. Regarding the effect on cell death signaling, we examined the expression of RIPK3 in Huh7 cells in vitro. When Huh7 cells were treated with sorafenib, increased expression of RIPK3 was observed by western blot and RT-PCR. Next, we treated Huh7 cells with sorafenib in combination with necroptosis inhibitor necrostatin-1. Necrostatin-1 attenuated the effect of sorafenib and increased the cell viability, which raises the possibility that necroptosis pathway is involved in the action mechanism of sorafenib.
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