2015 Fiscal Year Final Research Report
Antitumor activity of aromatase inhibitor and molecular targeted drugs in endometrial cancer and endometrial stromal sarcoma
| Project/Area Number |
25861471
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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 |
Obstetrics and gynecology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 抗腫瘍効果 / 子宮体癌 / 分子標的治療薬 |
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| Outline of Final Research Achievements |
Following the exposure to olaparib, a PARP inhibitor, cleaved-PARP was induced and the induction level was increased chronologically in the HEC-6 cells. Flow cytometric analysis revealed that olaparib markedly increased the sub-G1 population in HEC-6 cells. On the analysis using DS-7423, a dual inhibitor of PI3K and mTOR, all the nine ovarian clear cell adenocarcinoma(OCCA) cell lines were sensitive for DS-7423. In mouse xenograft models, DS-7423 suppressed the tumor growth of OCCA in a dose-dependent manner. The anti-tumor effect of DS-7423 was stronger in xenografts which the basal level of p-Akt was high. In addition, we examined the anti-tumor effect of voxtalisib (a PI3K/mTOR inhibitor) and/or pimasertib (a MEK inhibitor) in endometrial cancer cell lines. A combination of both compounds caused a synergistic antitumor effect in 6 out of 12 endometrial cancer cell lines. Flow cytometric analysis showed that this combination significantly increased the population of G1 cells.
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| Free Research Field |
婦人科腫瘍学
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