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2023 年度 実施状況報告書

癌幹細胞の老化回復におけるマイトファジーの役割

研究課題

研究課題/領域番号 23KF0268
研究機関長崎大学

研究代表者

李 桃生  長崎大学, 原爆後障害医療研究所, 教授 (50379997)

研究分担者 YAN CHEN  長崎大学, 原爆後障害医療研究所, 外国人特別研究員
研究期間 (年度) 2023-11-15 – 2026-03-31
キーワードCancer stem cells / Mitophagy / Senescence
研究実績の概要

Human HCT116 colorectal cancer cells were used in this study. To induce cellular senescence, HCT116 cells were treated with doxorubicin. At 7 days after doxorubicin treatment, HCT116 cells were stained strongly positive for senescence-associated β-galactosidase, suggesting the induction of senescent cells. Furthermore, the expression of p21, one of the most well-established senescence markers, was significantly higher in the doxorubicin-induced senescent HCT116 cells than in the untreated HCT116 cells. In the meantime, doxorubicin treatment also significantly inhibited the growth of HCT116 cells.
The expression of DNA damage indicators and cell cycle regulators are also determined. The expression of γH2AX, cyclin D1, and cyclin E1 were significantly higher in the doxorubicin-induced senescent HCT116 cells than in the untreated HCT116 cells, indicating enhanced DNA damage and cell cycle arrest in the doxorubicin-induced senescent HCT116 cells.
To investigate the reversibility, doxorubicin-induced senescent HCT116 cells were cultured in the medium without doxorubicin. Interestingly, some senescent HCT116 cells return to a proliferative state after 7 days of culture. Our data indicate the high plasticity of senescent cancer cells.

現在までの達成度 (区分)
現在までの達成度 (区分)

2: おおむね順調に進展している

理由

Our data showed that doxorubicin treatment induced cellular senescence in the HCT116 cells. Moreover, the doxorubicin-induced senescent HCT116 cells were able to return into a proliferative state. About the detailed mechanism, we have also started to investigate, such as DNA damage and cell cycle arrest.

今後の研究の推進方策

To further understand the role of mitophagy in regulating the plasticity of senescent cancers, we will:
1. Evaluate the mitophagy activity, mitochondrial function, and energy metabolism activity.
2. Confirm the role of mitophagy in regulating the reversal of senescent cancer cells by manipulating mitophagy activity.
3. Verify the effects of mitophagy-associated molecules in regulating the reversal of senescent cancer cells in mouse tumor models by evaluating the mitophagy activity and senescent/proliferative populations of cancer cells.

次年度使用額が生じた理由

As some existing reagents and antibodies in our department were used in this study, it resulted in an incurring amount to be used next fiscal year.
The incurring amount will be used for the cost of antibodies and kits for biochemical analysis to be carried out in the next fiscal year.

URL: 

公開日: 2024-12-25  

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