| Project/Area Number |
17K16832
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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) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 分子標的薬 / 卵巣癌 / 子宮体癌 / アポトーシス / 婦人科悪性腫瘍 / Bcl-2 family / PI3K/mTOR阻害薬 / MDM2阻害薬 / 明細胞癌 |
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| Outline of Final Research Achievements |
We investigated the antitumor effects of molecular targeting drugs related to apoptosis in gynecologic tumors. Addition of BH3 mimics BT 737 to endometrial and ovarian cancer cell lines inhibited cell proliferation and cell cycle analysis revealed the induction of apoptosis. In addition, the combination with the molecularly targeted drug PI3K / mTOR co-inhibitor showed a synergistic effect. We considered that the combination of MDM2 inhibitor and mTOR inhibitor could be another novel therapeutic option for ovarian clear cell carcinoma and we confirmed cell proliferation inhibitory effects using cell lines. We also confirmed cell growth suppression and apoptosis induction in subcutaneous tumor models of nude mice. The combination of MDM2 inhibitor and mTOR inhibitor showed significant cell growth suppression effects compared to each single agent.
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| Academic Significance and Societal Importance of the Research Achievements |
卵巣癌は抗癌剤耐性を獲得し再発を繰り返す難治性の悪性腫瘍であり、子宮体癌は再発時の抗癌剤の選択肢が限られていることから、新規の治療戦略が求められている。これらの婦人科悪性腫瘍ではBcl-2 familyやMDM2、p53、PI3K/ｍTORをはじめとするアポトーシスに関連する経路の異常が知られており、この経路をターゲットとした分子標的治療は新規治療法の選択肢となりうる。我々は本研究を通してBH3模倣薬、MDM2阻害剤、mTOR阻害剤の抗腫瘍薬としての可能性を明らかにした。
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