| Project/Area Number |
24791171
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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 |
Dermatology
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| Research Institution | Iwate Medical University |
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Principal Investigator |
AKASAKA K 岩手医科大学, 医学部, 研究員 (90552753)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 悪性黒色腫 / BCL2 / BCLxL / 抗微小管薬 / 皮膚腫瘍学 / MCL1 / apoptosis |
|---|
| Research Abstract |
Previous studies have suggested a link between TUBB3 overexpression and paclitaxel resistance through alterations in the properties of the mitotic spindle. We found that paclitaxel treatment induced temporary mitotic arrest in 7 melanoma cell lines irrespective of the TUBB3 level, suggesting that TUBB3 had no significant influence on spindle properties. On the other hand, the amount of BCL2, an anti-apoptotic protein, was well correlated with paclitaxel resistance. Treatment of the paclitaxel-resistant cell lines with ABT-737, an inhibitor of BCL2 and BCLxL, or simultaneous knock-down of BCL2 and BCLxL dramatically increased the cells' sensitivity, while knock-down of MCL1, another member of the BCL2 family, had only a minimal effect. Our results suggest that the paclitaxel sensitivity of melanoma cells is attributable to apoptosis susceptibility rather than a change in spindle properties and that BCL2 and BCLxL play a pivotal role in the former.
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