| Project/Area Number |
15K19331
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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 | The University of Tokushima |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | sorafenib / ソラフェニブ / 耐性 |
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| Outline of Final Research Achievements |
The mechanism of resistance of hepatocellular carcinoma (HCC) to sorafenib is unknown. Accordingly, we established sorafenib-resistant HCC cells and investigated the mechanism of resistance to sorafenib. Sorafenib-resistant cell lines were established from the HCC cell line PLC/PRF5. Western blot analysis of signal transduction-related proteins showed no significant differences in expression of AKT/pAKT, mTOR/pmTOR, or ERK/pERK between the 2 resistant clones versus parent cells. Likewise, when expression of membrane transporter proteins was determined, there were no significant differences between resistant clones and parent cells. However, the expression levels of MRP3 in the 2 resistant clones were significantly higher than that of parent cells. When MRP3 gene was knocked down by siRNA in PLCPRF5-R2 cells, the sensitivity of the cells to sorafenib was restored. Our data demonstrate that the efflux transporter MRP3 plays an important role in resistance to sorafenib in HCC cells.
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