The involvement of sphingolipid metabolism in anticancer agent - resistant melanoma cells
| Project/Area Number |
15K08094
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Medical pharmacy
|
|---|
| Research Institution | Gifu University |
|---|
Principal Investigator |
Seishima Mariko 岐阜大学, 大学院医学系研究科, 教授 (00171314)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
藤澤 智美 岐阜大学, 大学院医学系研究科, 非常勤講師 (20585583)
加納 宏行 岐阜大学, 大学院医学系研究科, 准教授 (40566494)
|
|---|
| Project Period (FY) |
2015-04-01 – 2018-03-31
|
| Project Status |
Completed (Fiscal Year 2017)
|
| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
|---|
| Keywords | 悪性黒色腫 / 抗がん剤耐性 / FTY720 / BRAF阻害薬 / スフィンゴ脂質代謝 / S1P受容体アンタゴニスト / 抗がん耐性 |
|---|
| Outline of Final Research Achievements |
We investigated the effects of combination of FTY720, phosphorylated and binds to sphingosine-1-phosphate receptors, and vemurafenib, an inhibitor of BRAFV600- mutant protein, on cell death induction and molecular mechanisms in vemurafenib-resistant melanoma cells. Combination of FTY720 and vemurafenib reduced cell viability and increased expression of cleaved PARP. The expression of phosphorylated ERK was decreased by this combination. Furthermore, vemurafenib-resistant SK-Mel-28 cells (R-SK-Mel) were established by culturing the SK-Mel-28 cell. In R-SK-Mel cells, the cell viability was also reduced and the expression of cleaved PARP was increased by the combination with FTY720 and vemurafenib. Moreover, the expression of phosphorylated ERK and Akt were reduced by this treatment. These findings suggest that FTY720 and vemurafenib synergistically induce cell death through downregulation of proliferation and survival signaling pathways in vemurafenib-resistant melanoma cells.
|
Report
(4 results)
Research Products
(34 results)
