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However, we have previously reported that PPIs may diminish the therapeutic effect of anti\u2010vascular 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.\u00a0The effects of PPI and vonoprazan on VEGF expression in cancer cells were compared by real\u2010time reverse transcription\u2010polymerase chain reaction\u00a0and ELISA. The interaction of vonoprazan and PPIs with transcriptional regulators by docking simulation analysis.\u00a0In various cancer cell lines, including the human colorectal cancer cell line (LS174T), PPI increased VEGF messenger\u00a0RNA 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\u2010\u03b1), one of the transcriptional regulators of VEGF, compared to PPI. Although the PPI\u2010induced increase in VEGF expression was counteracted by pharmacological ER\u2010\u03b1 inhibition, the effect of vonoprazan on VEGF expression was unchanged.\u00a0Vonoprazan 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\u2010VEGF cancer chemotherapy.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ddr.22013","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T05:19:57Z","timestamp":1670563197000},"page":"75-83","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Differential effects of proton pump inhibitors and vonoprazan on vascular endothelial growth factor expression in cancer cells"],"prefix":"10.1002","volume":"84","author":[{"given":"Rie","family":"Ando\u2010Matsuoka","sequence":"first","affiliation":[{"name":"Department of Clinical 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