Differential effects of proton pump inhibitors and vonoprazan on vascular endothelial growth factor expression in cancer cells

• Material Type: 博士論文
• Title: Differential effects of proton pump inhibitors and vonoprazan on vascular endothelial growth factor expression in cancer cells
• Author/Editor: Ando-Matsuoka, Rie; Yagi, Kenta; Takaoka, Mayu; Sakajiri, Yuko; Shibata, Tomokazu; Sawada, Ryusuke; Maruo, Akinori; Miyata, Koji; Aizawa, Fuka; Hamano, Hirofumi; Niimura, Takahiro; Izawa-Ishizawa, Yuki; Goda, Mitsuhiro; Sakaguchi, Satoshi; Zamami, Yoshito; Yamanishi, Yoshihiro; Ishizawa, Keisuke
• Author Heading: Ando-Matsuoka, Rie; Yagi, Kenta; Takaoka, Mayu; Sakajiri, Yuko; Shibata, Tomokazu; Sawada, Ryusuke; Maruo, Akinori; Miyata, Koji; Aizawa, Fuka; Hamano, Hirofumi; Niimura, Takahiro; Izawa-Ishizawa, Yuki; Goda, Mitsuhiro; Sakaguchi, Satoshi; Zamami, Yoshito; Yamanishi, Yoshihiro; Ishizawa, Keisuke
• Publication, Distribution, etc.: Wiley
• Publication Date: 2022-12-09; 84 1
• Publication Date (W3CDTF): 2022-12-09
• Alternative Title: がん細胞におけるvascular endothelial growth factor発現に対するプロトンポンプ阻害剤とボノプラザンの効果の違い; Effects of PPIs and vonoprazan on VEGF expression in cancer cells
• Degree grantor/type: 徳島大学
• Date Granted: 2023-03-23
• Date Granted (W3CDTF): 2023-03-23
• Dissertation Number: 甲第3699号
• Degree Type: 博士（医学）
• Text Language Code: eng
• Subject Heading: Proton pump inhibitors; vonoprazan; lansoprazole; fulvestrant; vascular endothelial growth factor
• Target Audience: 一般
• Note (General): Background. Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion, used as first-line agents in treating peptic ulcers. However, we have previously reported that PPIs may diminish the therapeutic effect of anti-vascular endothelial growth factor (VEGF) drugs in patients with cancer. In this study, we explored the effects of vonoprazan, a novel gastric acid secretion inhibitor used for the treatment of peptic ulcers, on the secretion of VEGF in cancer cells and attempted to propose it as an alternative PPI for cancer chemotherapy. Methods. The effects of PPI and vonoprazan on VEGF expression in cancer cells were compared by real-time rt-PCR and ELISA. The interaction of vonoprazan and PPIs with transcriptional regulators by docking simulation analysis. Results. In various cancer cell lines, including the human colorectal cancer cell line (LS174T), PPI increased VEGF mRNA expression and VEGF protein secretion, while this effect was not observed with vonoprazan. Molecular docking simulation analysis showed that vonoprazan had a lower binding affinity for estrogen receptor alpha (ER-α), one of the transcriptional regulators of VEGF, compared to PPI. Although the PPI-induced increase in VEGF expression was counteracted by pharmacological ER-α inhibition, the effect of vonoprazan on VEGF expression was unchanged. Conclusions. Vonoprazan does not affect VEGF expression in cancer cells, which suggests that vonoprazan might be an alternative to PPIs, with no interference with the therapeutic effects of anti-VEGF cancer chemotherapy.
• Persistent ID (NDL): info:ndljp/pid/13235156; https://dl.ndl.go.jp/pid/13235156
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• Date Accepted (W3CDTF): 2024-01-19T16:23:14+09:00
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• Periodical Title (URI): http://repo.lib.tokushima-u.ac.jp/118289
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