The cumulative antitumor effects of regorafenib and radiotherapy in hepatocellular carcinoma.

Autor: Kuang S; 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., Zhang J; 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., Huang N; 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., Zhang J; 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., Chen B; 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., Wang L; 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., Liu M; Laboratory of Cell and Molecular Biology & State Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2024 Sep; Vol. 63 (9), pp. 1738-1749. Date of Electronic Publication: 2024 Jun 05.
DOI: 10.1002/mc.23769
Abstrakt: Regorafenib is a second-line standard treatment for hepatocellular carcinoma (HCC). However, the efficacy of regorafenib is often limited due to drug resistance, individual differences among patients, and irrational drug use. Radiotherapy (RT) is an important method of localized HCC treatment, and combining RT with other therapies may exert a synergetic antitumor effect. Platelet-derived growth factor receptor-like (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. The 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. The combination treatment significantly inhibited cell proliferation and promoted apoptosis both in vitro and in vivo. PDGFRL, 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. This 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.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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