細胞転換によるがん細胞の薬剤感受性化メカニズムの解析

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Author: 加藤, 優

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Publication date: 2022

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Note (General)：: type:text細胞は、その生存環境に適応するために細胞転換する。本研究ではヒト大腸がん由来のHCT116細胞にEMTを誘導したEMT細胞を用いて、細胞転換時の薬剤感受性の変動機構について研究し、EMT細胞はglutathione peroxidase 4(GPX4)阻害剤に高感受性を示すことを明...

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科研費研究者番号 : 80847864

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Material Type: 文書・図像類
Title: 細胞転換によるがん細胞の薬剤感受性化メカニズムの解析
Author/Editor: 加藤, 優
Author Heading: 加藤, 優
Publication Date: 2022
Publication Date (W3CDTF): 2022
Alternative Title: サイボウテンカンニヨルガンサイボウノヤクザイカンジュセイカメカニズムノカイセキ
Saibō tenkan ni yoru gansaibō no yakuzai kanjuseika mekanizumu no kaiseki
Analysis of the mechanism of drug sensitization of cancer cells with cell transition
Periodical title: 科学研究費補助金研究成果報告書
Text Language Code: jpn
eng
Subject Heading: 細胞転換,上皮間葉転換,スフェロイド,glutathione peroxidase 4,glutathione
Target Audience: 一般
Note (General): type:text
細胞は、その生存環境に適応するために細胞転換する。本研究ではヒト大腸がん由来のHCT116細胞にEMTを誘導したEMT細胞を用いて、細胞転換時の薬剤感受性の変動機構について研究し、EMT細胞はglutathione peroxidase 4(GPX4)阻害剤に高感受性を示すことを明らかにした。このEMT細胞のRSL3高感受性には、細胞内glutathioneの低下が関与していた。次に、通常培養よりも生体内に近いスフェロイド培養時に高感受性化する薬剤を探索し、BET阻害剤のdBET6を同定した。dBET6はEMT細胞において通常培養、スフェロイド培養の両方でRSL3への感受性を増大させた。 Cells undergo cellular transition to adapt to their survival environment. In this study, we investigated the mechanism of variation in drug sensitivity during cell transition using EMT cells that were transduced SLUG and SNAIL in HCT116 cells derived from human colorectal cancer. We found that EMT cells showed high sensitivity to glutathione peroxidase 4 (GPX4) inhibitors. This high sensitivity of EMT cells to RSL3 was associated with a decrease in intracellular glutathione that is a substrate of GPX4. Next, we searched for drugs that are more sensitive to RSL3 in spheroid culture, which is closer to in vivo than in normal culture. Then we found that dBET6, a BET inhibitor, strongly prevented cell growth during spheroid culture. Moreover, dBET6 increased sensitivity to RSL3 in EMT cells in both normal and spheroid culture.
研究種目 : 若手研究研究期間 : 2020～2022 課題番号 : 20K16339 研究分野 : 腫瘍学、分子生物学
Access Restrictions: 限定公開
Related Material: 科研費研究者番号 : 80847864
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 慶應義塾大学 : 慶應義塾大学学術情報リポジトリ