The Angiotensin II Receptor Blocker Losartan Sensitizes Human Liver Cancer Cells to Lenvatinib-Mediated Cytostatic and Angiostatic Effects.

• 資料種別: 博士論文
• タイトル: The Angiotensin II Receptor Blocker Losartan Sensitizes Human Liver Cancer Cells to Lenvatinib-Mediated Cytostatic and Angiostatic Effects.
• 著者・編者: Takagi, Hirotetsu; Kaji, Kosuke; Nishimura, Norihisa; Ishida, Koji; Ogawa, Hiroyuki; Takaya, Hiroaki; Kawaratani, Hideto; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Mitoro, Akira; Yoshiji, Hitoshi
• 著者標目: Takagi, Hirotetsu; Kaji, Kosuke; Nishimura, Norihisa; Ishida, Koji; Ogawa, Hiroyuki; Takaya, Hiroaki; Kawaratani, Hideto; Moriya, Kei; Namisaki, Tadashi; Akahane, Takemi; Mitoro, Akira; Yoshiji, Hitoshi
• 出版事項: MDPI
• 出版年月日等: 2021-03-05
• 出版年（W3CDTF）: 2021-03-05
• 並列タイトル等: アンジオテンシンII 受容体拮抗薬であるロサルタンは、レンバチニブによるヒト肝癌細胞への 細胞増殖抑制性および血管新生抑制効果の感性を向上させる
• タイトル（掲載誌）: Cells
• 巻号年月日等（掲載誌）: 10 3
• 掲載巻: 10
• 掲載号: 3
• 掲載ページ: Article No.575-
• ISSN（掲載誌）: ISSN : 2073-4409
• 授与機関名: 奈良県立医科大学
• 授与年月日: 2022-03-15
• 報告番号: 甲第813号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: HCC; VEGF; angiotensin-II; angiogenesis; lenvatinib
• 対象利用者: 一般
• 一般注記: type:Thesis; Molecular targeted therapy with lenvatinib is commonly offered to advanced hepatocellular carcinoma (HCC) patients, although it is often interrupted by adverse effects which require a reduction in the initial dose. Thus, an alternative lenvatinib-based therapy to compensate for dose reduction is anticipated. This study aimed to assess the effect of combination of low-dose of lenvatinib and the angiotensin-II (AT-II) receptor blocker losartan on human HCC cell growth. In vitro studies found that losartan suppressed the proliferation by inducing G1 arrest and caused apoptosis as indicated by the cleavage of caspase-3 in AT-II-stimulated HCC cell lines (Huh-7, HLE, and JHH-6). Losartan attenuated the AT-II-stimulated production of vascular endothelial growth factor-A (VEGF-A) and interleukin-8 and suppressed lenvatinib-mediated autocrine VEGF-A production in HCC cells. Moreover, it directly inhibited VEGF-mediated endothelial cell growth. Notably, the combination of lenvatinib and losartan augmented the cytostatic and angiostatic effects of the former at a low-dose, reaching those achieved with a conventional dose. Correspondingly, a HCC tumor xenograft assay showed that the oral administration of losartan combined with lenvatinib reduced the subcutaneous tumor burden and intratumor vascularization in BALB/c nude mice. These findings support that this regimen could be a viable option for patients intolerant to standard lenvatinib dosage.; 博士（医学）・甲第813号・令和4年3月15日; © 2021 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:Cells Vol.10 No.3 Article No.575 (2021 Mar); identifier:20734409; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/3996; identifier:Cells, 10(3): Article No.575
• 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/cells10030575
• 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

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http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3996/1/01%e7%94%b2813%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/10564/3996/2/02%e7%94%b2813%e5%af%a9%e6%9f%bb%e8%a6%81%e6%97%a8.pdf fulltext

http://ginmu.naramed-u.ac.jp/dspace/bitstream/10564/3996/3/03%e7%94%b2813%e6%9c%ac%e6%96%87.pdf fulltext