2023 Fiscal Year Final Research Report
Establishment of a method for inhibiting the infiltration and metastasis of malignant melanoma by targeting heme oxygenase.
| Project/Area Number |
21K06907
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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 49020:Human pathology-related
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| Research Institution | Iwate Medical University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
前沢 千早 岩手医科大学, 医歯薬総合研究所, 教授 (10326647)
天野 博雄 岩手医科大学, 医学部, 教授 (70302487)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | NFE2L2 / HO-1 / GPX4 / ヘミン |
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| Outline of Final Research Achievements |
In this study, we focused on two pathways among the numerous NFE2L2 pathways: pathway 1 involving the aforementioned heme oxygenase and pathway 2 involving GPX4, and investigated the effects of changes in cellular heme levels on the invasive and survival abilities of melanoma.
First, regarding pathway 1, we examined the invasive ability of melanoma cells by increasing cellular heme levels through administration of heme. As a result, a significant decrease in melanoma invasion was observed. Next, regarding pathway 2, we investigated the combined effects of a GPX4 inhibitor and heme. As a result, significant reduction in melanoma survival was observed in the heme administration group. Therefore, the effectiveness of heme as a melanoma treatment strategy is suggested.
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| Free Research Field |
分子生物学
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| Academic Significance and Societal Importance of the Research Achievements |
メラノーマ治療では分子標的治療薬ベムラフェニブが注目されるが、適用対象はBRAFV600E変異をもつものに限られる。しかし日本人においてBRAFV600E変異タイプは25％以下であり、欧米人に比べ低い。本研究では、ベムラフェニブが奏効しないメラノーマ細胞株につき、腫瘍細胞の浸潤抑制においてはNFE2L2とその制御下にある下流因子HO-1が候補となること、また現在、急性ポルフィリン治療薬として実際に使用されているヘミンが、これら因子を介して有意に浸潤抑制すること、また同じくNFE2L2の制御下にあるGPX4の阻害による抗腫瘍細胞効果は、ヘミンにより増強されることを明らかにした。
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