| Project/Area Number |
18K09288
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
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| Research Institution | University of Occupational and Environmental Health, Japan |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
上田 豊 大阪大学, 医学系研究科, 講師 (10346215)
小林 栄仁 大阪大学, 医学系研究科, 助教 (50614773)
松崎 慎哉 大阪大学, 医学部附属病院, 助教 (00467565)
中川 慧 大阪大学, 医学系研究科, 助教 (30650593)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 卵巣がん / プラチナ耐性 / 核酸医薬 / 明細胞癌 / 卵巣癌 / プラチナ感受性 / アネキシン / アネキシンA4 |
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| Outline of Final Research Achievements |
Platinum agents are widely used as chemotherapy for ovarian cancer. Therefore, platinum resistance is a major problem. We found that elevated expression levels of annexin A4 (ANXA4) in clear cell carcinoma of the ovary (CCC) was associated with platinum chemoresistance by promoting platinum efflux. Based on these results, we designed an oligonucleotide and try to suppress the expression of ANXA4 using it. We created two candidates antisense oligos (ASOs) with high knockdown efficiency (knockdown rates: 96.9% and 94.5%). The ANXA4 ASO-transfected cells showed increased sensitivity to the platinum drugs, cisplatin or carboplatin (42.5% and 55.2%, respectively) and increased intracellular accumulation of platinum drugs (34.0% and 48.4%, respectively). In experiments using model mice, the combination of ANXA4 ASO and cisplatin enhanced the anti-tumor effect. These results suggest that ANXA4 ASO may be a potential therapeutic option for ovarian clear cell carcinoma.
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| Academic Significance and Societal Importance of the Research Achievements |
抗がん剤が効かないタイプの卵巣癌に対して、アネキシンA4蛋白を抑制する核酸と抗がん剤の併用が実験のなかでは腫瘍縮小効果を示した。さらに研究を進めることによって将来新たな治療薬の候補となる可能性があり、難治性と考えられている卵巣がん患者さんの予後改善に貢献することが期待される。
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