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Radiotherapy (RT) is an important method of localized HCC treatment, and combining RT with other therapies may exert a synergetic antitumor effect. Platelet\u2010derived growth factor receptor\u2010like (PDGFRL) is a tumor suppressor in various solid tumors. However, the function of PDGFRL in HCC is still unknown. In this study, we explored whether regorafenib and RT exert a synergetic effect on the treatment of HCC.\u00a0The antitumor effect and mechanisms of the combination of regorafenib and RT were verified in a xenograft mouse model in vivo and in HCC cells in vitro.\u00a0The combination treatment significantly inhibited cell proliferation and promoted apoptosis both in vitro and in vivo.\u00a0PDGFRL, a potential target of regorafenib, was increased after cumulative treatment in HCC cells, and PDGFRL suppressed HCC cell proliferation and promoted apoptosis by inhibiting STAT3 pathway activation. Furthermore, the cumulative antitumor effect was dependent on the upregulated expression of PDGFRL and inhibition of STAT3 signaling pathway activation in HCC cells.\u00a0This study increased the understanding of the molecular mechanism underlying the effect of regorafenib plus RT on HCC and provided a theoretical basis for the clinical practice of HCC.<\/jats:p>","DOI":"10.1002\/mc.23769","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T13:36:02Z","timestamp":1717594562000},"page":"1738-1749","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["The cumulative antitumor effects of regorafenib and radiotherapy in hepatocellular carcinoma"],"prefix":"10.1002","volume":"63","author":[{"given":"Shuwen","family":"Kuang","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liming","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary Surgery, National Cancer Center\/National Clinical Research Center for Cancer\/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7364-6318","authenticated-orcid":false,"given":"Mei","family":"Liu","sequence":"additional","affiliation":[{"name":"Laboratory of Cell and Molecular Biology &amp; 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