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AMCoR:Asahikawa Medical University Collection and Research (旭川医科大学学術成果リポジトリ)は、本学で生産された電子的な知的生産物(学術雑誌論文の原稿・教材・学術資料など)を保存し、原則的に無償で発信するためのインターネット上の保管庫です。

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閲覧数:313
ID 20210630_K561
アイテムタイプ Article
このアイテムを表示する
本文 K561 Iwama Takuya_TD.pdf
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Size : 6.7 MB
Last updated : Dec 23, 2021
Downloads : 100

Total downloads since Dec 23, 2021 : 100
タイトル Bacteria-derived ferrichrome inhibits tumor progression in sporadic colorectal neoplasms and colitis-associated cancer (細菌由来のフェリクロームは散発性大腸腫瘍および大腸炎関連癌の腫瘍進行を抑制する)
著者
岩間, 琢哉 (Iwama, Takuya)
上位タイトル
Cancer cell international Vol.21, No.1  (2020. 1) ,p.21-
識別番号
ISSN
1475-2867
DOI 10.1186/s12935-020-01723-9
その他
PMID:33407519
Cancer Cell Int.2021 Jan 6;21(1):21
博士論文情報
学位授与番号 10107A561
学位授与年月日 2021-06-30
学位名 博士(医学)
学位授与機関 旭川医科大学
抄録 Background: Colorectal cancers develop through several pathways, including the adenoma-carcinoma sequence and colitis-associated carcinogenesis. An altered intestinal microflora has been reported to be associated with the development and progression of colorectal cancer via these pathways. We identified Lactobacillus casei-derived ferrichrome as a mediator of the bacterial anti-tumor effect of colorectal cancer cells through the upregulation of DDIT3. In this study, we investigated the anti-tumor effects of ferrichrome on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer.

Methods: SRB and MTT assays were performed to assess growth inhibition in vitro. Eighteen organoids were prepared from biopsy specimens obtained by colonoscopy. An AOM-DSS carcinogenesis model and xenograft model of colorectal cancer cells were generated for the assessment of the tumor suppressive effect of ferrichrome in vivo.

Results: Ferrichrome inhibited the cell growth of colorectal cancer cells in vitro and in in vivo xenograft models. Ferrichrome exerted a strong tumor-suppressive effect that was superior to that of currently available anti-tumor agents, including 5-FU and cisplatin, both in vitro and in vivo. The tumor-suppressive effect of the combination of ferrichrome and 5-FU was superior to that of single treatment with either drug. The tumor suppressive effects of ferrichrome were confirmed through the upregulation of DDIT3 in patient-derived organoids of adenoma and carcinoma. Ferrichrome inhibited the tumor progression in the AOM-DSS model while exhibiting no anti-inflammatory effect in the DSS-colitis model, suggesting that ferrichrome inhibited cancer cells, but not a precancerous condition, via the colitis-associated pathway.

Conclusions: Ferrichrome exerts a tumor suppressive effect on precancerous conditions and cancer cells associated with sporadic as well as colitis-associated colorectal cancer. The anti-tumor effect of ferrichrome was mediated by the upregulation of DDIT3, and was superior to that of 5-FU or cisplatin. These results suggest that Lactobacillus brevis-derived ferrichrome may be a candidate anti-tumor drug for the treatment of colorectal neoplasms.
キーワード
Colorectal cancer
DDIT3
Ferrichrome
Organoid
Probiotics
言語
eng
資源タイプ application/pdf
ジャンル Thesis or Dissertation
著者版フラグ ETD
Index
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/ Public / 学位論文
/ Public / 学位論文 / 博士論文2020.3~
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