Atorvastatin Augments Gemcitabine-Mediated Anti-Cancer Effects by Inhibiting Yes-Associated Protein in Human Cholangiocarcinoma Cells.

• 資料種別: 博士論文
• タイトル: Atorvastatin Augments Gemcitabine-Mediated Anti-Cancer Effects by Inhibiting Yes-Associated Protein in Human Cholangiocarcinoma Cells.
• 著者・編者: Kitagawa, Koh; Moriya, Kei; Kaji, Kosuke; Saikawa, Soichiro; Sato, Shinya; Nishimura, Norihisa; Namisaki, Tadashi; Akahane, Takemi; Mitoro, Akira; Yoshiji, Hitoshi
• 著者標目: Kitagawa, Koh; Moriya, Kei; Kaji, Kosuke; Saikawa, Soichiro; Sato, Shinya; Nishimura, Norihisa; Namisaki, Tadashi; Akahane, Takemi; Mitoro, Akira; Yoshiji, Hitoshi
• 出版事項: MDPI
• 出版年月日等: 2020-10-14
• 出版年（W3CDTF）: 2020-10-14
• 並列タイトル等: スタチンはYAP制御を介してゲムシタビンの肝内胆管癌抑制効果を増強させる
• タイトル（掲載誌）: International journal of molecular sciences
• 巻号年月日等（掲載誌）: 21 20
• 掲載巻: 21
• 掲載号: 20
• 掲載ページ: Article No.7588-
• ISSN（掲載誌）: ISSN : 1422-0067
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2021-03-15
• 報告番号: 甲第778号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: atorvastatin; HMG-CoA reductase; gemcitabine; TEAD transcriptional activation; yes-associated protein; cholangiocarcinoma
• 対象利用者: 一般
• 一般注記: type:Thesis; Cholangiocarcinoma (CCA) is associated with high mortality rates because of its resistance to conventional gemcitabine-based chemotherapy. Hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors (statins) reportedly exert anti-cancer effects in CCA and lower the risk of CCA; however, the underlying mechanism of these effects remains unclear. The proliferative and oncogenic activities of the transcriptional co-activator Yes-associated protein (YAP) are driven by its association with the TEA domain (TEAD) of transcription factors; thereby, upregulating genes that promote cell growth, inhibit apoptosis, and confer chemoresistance. This study investigated the effects of atorvastatin in combination with gemcitabine on the progression of human CCA associated with YAP oncogenic regulation. Both atorvastatin and gemcitabine concentration-dependently suppressed the proliferation of HuCCT-1 and KKU-M213 human CCA cells. Moreover, both agents induced cellular apoptosis by upregulating the pro-apoptotic marker BAX and downregulating the anti-apoptotic markers MCL1 and BCL2. Atorvastatin also significantly decreased the mRNA expression of the TEAD target genes CTGF, CYR61, ANKRD1, and MFAP5 in both CCA cell lines. A xenograft tumor growth assay indicated that atorvastatin and gemcitabine potently repressed human CCA cell-derived subcutaneous tumor growth by inhibiting YAP nuclear translocation and TEAD transcriptional activation. Notably, the anti-cancer effects of the individual agents were significantly enhanced in combination. These results indicate that gemcitabine plus atorvastatin could serve as a potential novel treatment option for CCA.; 博士（医学）・甲第778号・令和3年3月15日; © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).; identifier:International journal of molecular sciences Vol.21 No.20 Article No.7588 (2020 Oct); identifier:14220067; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3902; identifier:International journal of molecular sciences, 21(20): Article No.7588
• オンライン閲覧公開範囲: インターネット公開
• 関連情報（DOI）: 10.3390/ijms21207588
• 連携機関・データベース: 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
• 提供元機関・データベース: 奈良県立医科大学 : 奈良県立医科大学機関リポジトリ GINMU

目次

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3902/1/01%e7%94%b2778%e6%9c%ac%e6%96%87%e3%81%ae%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3902/2/02%e7%94%b2778%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3902/3/03%e7%94%b2778%e6%9c%ac%e6%96%87.pdf fulltext