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111-2628-B-037-010"],"award-info":[{"award-number":["MOST 111-2628-B-037-010"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Ministry of Science and Technology, Taiwan","award":["MOST 111-2314-B-037-094 -MY3"],"award-info":[{"award-number":["MOST 111-2314-B-037-094 -MY3"]}],"id":[{"id":"https:\/\/ror.org\/02kv4zf79","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>5-FU-based chemoradiotherapy (CRT) and oxaliplatin-based CRT are commonly used therapies for advanced colorectal cancer (CRC). However, patients with a high expression of ERCC1 have a worse prognosis than those with a low expression. In this study, we investigated the effect of XPF\u2013ERCC1 blockers on chemotherapy and 5-FU-based CRT and oxaliplatin (OXA)-based CRT in colorectal cancer cell lines. We investigated the half-maximal inhibitory concentration (IC50) of 5-FU, OXA, XPF\u2013ERCC1 blocker, and XPF\u2013ERCC1 blocker, and 5-FU or OXA combined and analyzed the effect of XPF\u2013ERCC1 blocker on 5-FU-based CRT and oxaliplatin-based CRT. Furthermore, the expression of XPF and \u03b3-H2AX in colorectal cells was analyzed. In animal models, we combined the XPF\u2013ERCC1 blocker with 5-FU and OXA to investigate the effects of RC and finally combined the XPF\u2013ERCC1 blocker with 5-FU- and oxaliplatin-based CRT. In the IC50 analysis of each compound, the cytotoxicity of the XPF\u2013ERCC1 blocker was lower than that of 5-FU and OXA. In addition, the XPF\u2013ERCC1 blocker combined with 5-FU or OXA enhanced the cytotoxicity of the chemotherapy drugs in colorectal cells. Furthermore, the XPF\u2013ERCC1 blocker also increased the cytotoxicity of 5-FU-based CRT and OXA -based CRT by inhibiting the XPF product DNA locus. In vivo, the XPF\u2013ERCC1 blocker was confirmed to enhance the therapeutic efficacy of 5-FU, OXA, 5-FU-based CRT, and OXA CRT. These findings show that XPF\u2013ERCC1 blockers not only increase the toxicity of chemotherapy drugs but also increase the efficacy of combined chemoradiotherapy. In the future, the XPF\u2013ERCC1 blocker may be used to improve the efficacy of 5-FU- and oxaliplatin-based CRT.<\/jats:p>","DOI":"10.3390\/cells12111475","type":"journal-article","created":{"date-parts":[[2023,5,26]],"date-time":"2023-05-26T01:52:43Z","timestamp":1685065963000},"page":"1475","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["XPF\u2013ERCC1 Blocker Improves the Therapeutic Efficacy of 5-FU- and Oxaliplatin-Based Chemoradiotherapy in Colorectal Cancer"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9432-5284","authenticated-orcid":false,"given":"Ming-Yii","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Radiation Oncology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Center for Cancer Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2074-4096","authenticated-orcid":false,"given":"Yi-Jung","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Post Baccalaureate Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tian-Lu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wun-Ya","family":"Jhang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Chih","family":"Ke","sequence":"additional","affiliation":[{"name":"Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0817-1539","authenticated-orcid":false,"given":"Yi-Ting","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Pathology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Hsun","family":"Kuo","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7022-4315","authenticated-orcid":false,"given":"I-Ling","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Hsiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Post-Graduate Year Training, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1221-6584","authenticated-orcid":false,"given":"Chih-Hung","family":"Chuang","sequence":"additional","affiliation":[{"name":"Drug Development and Value Creation Research Center, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1002\/jso.21711","article-title":"The impact of preoperative chemoradiotherapy on advanced low rectal cancer","volume":"102","author":"Kao","year":"2010","journal-title":"J. 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