| 研究課題/領域番号 |
21K07921
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| 研究種目 |
基盤研究(C)
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| 配分区分 | 基金 |
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| 応募区分 | 一般 |
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| 審査区分 |
小区分53010:消化器内科学関連
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| 研究機関 | 大阪公立大学 (2022-2023)
大阪市立大学 (2021) |
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研究代表者 |
HOANG HAI 大阪公立大学, 大学院医学研究科, 研究員 (60623246)
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| 研究分担者 |
LE THITHANHTHUY 大阪公立大学, 大学院医学研究科, 准教授 (10572175)
河田 則文 大阪公立大学, 大学院医学研究科, 教授 (30271191)
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| 研究期間 (年度) |
2021-04-01 – 2025-03-31
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| 研究課題ステータス |
交付 (2023年度)
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| 配分額 *注記 |
4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2023年度: 1,170千円 (直接経費: 900千円、間接経費: 270千円)
2022年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2021年度: 1,690千円 (直接経費: 1,300千円、間接経費: 390千円)
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| キーワード | DNA methylation / CYGB promoter / Liver tumor / Huh-7 / DAC / Liver cancer / Cytoglobin / Promoter / Demethylation / liver tumor / pancreatic tumor |
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| 研究開始時の研究の概要 |
Cytoglobin (CYGB), an oxygen-binding and reactive oxygen species (ROS) scavenging protein, functions as a tumor suppressor and is inactivated in various cancers. This research aims to (i) examine the protective role of Cygb-overexpression in animal models of liver and pancreas carcinogenesis; (ii) investigate the frequency of DNA methylation of the CYGB promoter in malignant tissues from patients with liver or pancreatic cancers; (iii) targeted demethylation of the CYGB promoter to impair tumor growth. These results will provide the potential therapeutic application of anti-cancer therapy.
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| 研究実績の概要 |
Cytoglobin (CYGB) acts as a tumor suppressor gene. Restoration of CYGB expression was demonstrated in HCC cell lines treated with 1, 3, 5, and 10 uM 5-aza-2′- deoxycytidine (DAC). Interestingly, DAC treatment time- and dose-dependently restored CYGB expression at both mRNA and protein levels in SNU-387, HLE and Huh7, and at mRNA level in HepG2 cells while DAC did not induce CYGB expression in LX-2. Notably, after inducing CYGB expression in SNU-387, removal of DAC resulted in regressing of CYGB expression at both mRNA and protein levels. Next, we aim to elucidate the DAC is able to inhibit the tumor formation in mice injected with HCC cells.
Huh-7 cells were treated with DAC dose escalation from 1 to 10uM. After 3 weeks of DAC treatment, Huh-7 cells were subcutaneously injected into the right flanks in 9 nude mice. Untreated Huh-7 cells were injected into the left flanks as control.
All of 9 mice appeared big tumors in the left flanks by mean volume of 3570 mm3 while small tumors (mean 61 mm3) were observed in the right flanks injected with Huh-7 + DAC.
Therefore, demethylation of CYGB gene promoter by DAC may lead to cancer regression.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
3: やや遅れている
理由
I have worked at the other institution for 6 months from April to September 2023.
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| 今後の研究の推進方策 |
1- Analyze the tumor formed by Huh-7 cell injection: HE, IF staining.
2- In vitro, liver cancer cells will be investigated CCK8, migration assay, wound healing assay, over expressed CYGB.
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