Lauric acid overcomes hypoxia-induced gemcitabine chemoresistance in pancreatic ductal adenocarcinoma

• Material Type: 博士論文
• Title: Lauric acid overcomes hypoxia-induced gemcitabine chemoresistance in pancreatic ductal adenocarcinoma
• Author/Editor: Takagi, Tadataka; Fujiwara-Tani, Rina; Mori, Shiori; Kishi, Shingo; Nishiguchi, Yukiko; Sasaki, Takamitsu; Ogata, Ruiko; Ikemoto, Ayaka; Sasaki, Rika; Ohmori, Hitoshi; Luo, Yi; Bhawal, Ujjal Kumar; Sho, Masayuki; Kuniyasu, Hiroki
• Author Heading: Takagi, Tadataka; Fujiwara-Tani, Rina; Mori, Shiori; Kishi, Shingo; Nishiguchi, Yukiko; Sasaki, Takamitsu; Ogata, Ruiko; Ikemoto, Ayaka; Sasaki, Rika; Ohmori, Hitoshi; Luo, Yi; Bhawal, Ujjal Kumar; Sho, Masayuki; Kuniyasu, Hiroki
• Publication, Distribution, etc.: MDPI
• Publication Date: 2023-04; 24 8
• Publication Date (W3CDTF): 2023-04
• Alternative Title: 膵癌におけるラウリン酸による低酸素誘導性ゲムシタビン抵抗性の克服
• Degree grantor/type: 奈良県立医科大学
• Date Granted: 2024-03-14
• Date Granted (W3CDTF): 2024-03-14
• Dissertation Number: 甲第916号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: gemcitabine; drug resistance; hypoxia; mitochondria; pancreatic cancer
• Target Audience: 一般
• Note (General): type:Thesis; Although gemcitabine (GEM) is widely used in chemotherapy for pancreatic ductal adenocarcinoma (PDA), drug resistance restricts its clinical effectiveness. To examine the mechanism of GEM resistance, we established two GEM-resistant cell lines from human PDA cells by continuous treatment with GEM and CoCl2-induced chemical hypoxia. One resistant cell line possessed reduced energy production and decreased mitochondrial reactive oxygen species levels, while the other resistant cell line possessed increased stemness. In both cell lines, ethidium bromide-stained mitochondrial DNA levels decreased, suggesting mitochondrial DNA damage. Inhibition of hypoxiainducible factor-1 in both cell lines did not restore the GEM sensitivity. In contrast, treatment of both cell types with lauric acid (LAA), a medium-chain fatty acid, restored GEM sensitivity. These results suggest that decreased energy production, decreased mitochondrial reactive oxygen species levels, and increased stemness associated with mitochondrial damage caused by GEM lead to GEM resistance, and that hypoxia may promote this process. Furthermore, forced activation of oxidative phosphorylation by LAA could be a tool to overcome GEM resistance. Clinical verification of the effectiveness of LAA in GEM resistance is necessary in the future.; 権利情報：© 2023 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 (https://creativecommons.org/licenses/by/4.0/).; identifier:International Journal of Molecular Sciences. 2023 Apr, vol.24, no.8, article no.7506; identifier:1661-6596; identifier:http://ginmu.naramed-u.ac.jp/dspace/handle/10564/4367; identifier:International Journal of Molecular Sciences, 24(8): 7506
• Persistent ID (NDL): info:ndljp/pid/13722127; https://dl.ndl.go.jp/pid/13722127
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• Date Accepted (W3CDTF): 2024-07-05T22:06:56+09:00
• Format (IMT): application/pdf
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• Periodical Title (URI): http://hdl.handle.net/10564/4367
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp