Fucoidan inhibits EGFR redistribution and potentiates sorafenib to overcome sorafenib-resistant hepatocellular carcinoma
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although sorafenib is a standard first-line molecule-targeted drug against advanced HCC, the drug resistance development and adverse side effects usually limit its efficacy. This study investigated the ef...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S075333222200991X |
| _version_ | 1798003117641433088 |
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| author | Jialiang Luo Lei Li Zhengyumeng Zhu Bo Chang Fan Deng Di Wang Xiao Lu Daming Zuo Qingyun Chen Jia Zhou |
| author_facet | Jialiang Luo Lei Li Zhengyumeng Zhu Bo Chang Fan Deng Di Wang Xiao Lu Daming Zuo Qingyun Chen Jia Zhou |
| author_sort | Jialiang Luo |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although sorafenib is a standard first-line molecule-targeted drug against advanced HCC, the drug resistance development and adverse side effects usually limit its efficacy. This study investigated the effect of fucoidan on the sorafenib sensitivity of sorafenib-resistant human HCC cell line HepG2-SR established by long-time exposure of HepG2 to sorafenib. We demonstrated fucoidan combined with sorafenib synergistically promoted apoptosis and cell cycle arrest whereas inhibited cell migration in HepG2-SR cells. This combination treatment effectively suppressed the cellular epithelial growth factor receptor (EGFR) nuclear distribution and downstream gene transcription. Interestingly, fucoidan bound the cell surface EGFR, dampening EGFR translocation to lipid raft and further nuclear distribution, restoring the sorafenib sensitivity in HepG2-SR cells. Blocking fucoidan-EGFR interaction using EGFR antibody restrained the enhanced anti-tumor effects upon the combined administration. Besides, EGFR knockdown abolished the combination treatment-improved anti-tumor efficacy. This combination also suppressed in vivo xenograft tumor growth in nude mice. Our present study uncovered that fucoidan overcame sorafenib resistance in HCC via its interaction with cell membrane EGFR and further suppression of EGFR redistribution and downstream signaling in sorafenib-resistant cells. Overall, current results suggest that simultaneous treatment of fucoidan and sorafenib might serve as a potential therapeutic strategy against sorafenib-resistant HCC. |
| first_indexed | 2024-04-11T12:03:54Z |
| format | Article |
| id | doaj.art-44f8bb3f255b4885b6d2d375d0bb8dd9 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-11T12:03:54Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-44f8bb3f255b4885b6d2d375d0bb8dd92022-12-22T04:24:47ZengElsevierBiomedicine & Pharmacotherapy0753-33222022-10-01154113602Fucoidan inhibits EGFR redistribution and potentiates sorafenib to overcome sorafenib-resistant hepatocellular carcinomaJialiang Luo0Lei Li1Zhengyumeng Zhu2Bo Chang3Fan Deng4Di Wang5Xiao Lu6Daming Zuo7Qingyun Chen8Jia Zhou9Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China; Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, PR ChinaDepartment of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China; Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, PR ChinaDepartment of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China; Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, PR ChinaDepartment of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, PR ChinaDepartment of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China; Department of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, PR ChinaDepartment of Dermatology, Dermatology Hospital of Southern Medical University, Southern Medical University, Guangzhou, Guangdong, PR ChinaDepartment of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, PR ChinaDepartment of Medical Laboratory, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, Guangdong, PR ChinaMedical Research Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, PR China; Corresponding author.Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China; Key Laboratory of Functional Proteomics of Guangdong Province, Guangzhou, Guangdong, PR China; Corresponding author at: Department of Immunology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, PR China.Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although sorafenib is a standard first-line molecule-targeted drug against advanced HCC, the drug resistance development and adverse side effects usually limit its efficacy. This study investigated the effect of fucoidan on the sorafenib sensitivity of sorafenib-resistant human HCC cell line HepG2-SR established by long-time exposure of HepG2 to sorafenib. We demonstrated fucoidan combined with sorafenib synergistically promoted apoptosis and cell cycle arrest whereas inhibited cell migration in HepG2-SR cells. This combination treatment effectively suppressed the cellular epithelial growth factor receptor (EGFR) nuclear distribution and downstream gene transcription. Interestingly, fucoidan bound the cell surface EGFR, dampening EGFR translocation to lipid raft and further nuclear distribution, restoring the sorafenib sensitivity in HepG2-SR cells. Blocking fucoidan-EGFR interaction using EGFR antibody restrained the enhanced anti-tumor effects upon the combined administration. Besides, EGFR knockdown abolished the combination treatment-improved anti-tumor efficacy. This combination also suppressed in vivo xenograft tumor growth in nude mice. Our present study uncovered that fucoidan overcame sorafenib resistance in HCC via its interaction with cell membrane EGFR and further suppression of EGFR redistribution and downstream signaling in sorafenib-resistant cells. Overall, current results suggest that simultaneous treatment of fucoidan and sorafenib might serve as a potential therapeutic strategy against sorafenib-resistant HCC.http://www.sciencedirect.com/science/article/pii/S075333222200991XFucoidanSorafenib resistanceHepatocellular carcinomaEGFR |
| spellingShingle | Jialiang Luo Lei Li Zhengyumeng Zhu Bo Chang Fan Deng Di Wang Xiao Lu Daming Zuo Qingyun Chen Jia Zhou Fucoidan inhibits EGFR redistribution and potentiates sorafenib to overcome sorafenib-resistant hepatocellular carcinoma Biomedicine & Pharmacotherapy Fucoidan Sorafenib resistance Hepatocellular carcinoma EGFR |
| title | Fucoidan inhibits EGFR redistribution and potentiates sorafenib to overcome sorafenib-resistant hepatocellular carcinoma |
| title_full | Fucoidan inhibits EGFR redistribution and potentiates sorafenib to overcome sorafenib-resistant hepatocellular carcinoma |
| title_fullStr | Fucoidan inhibits EGFR redistribution and potentiates sorafenib to overcome sorafenib-resistant hepatocellular carcinoma |
| title_full_unstemmed | Fucoidan inhibits EGFR redistribution and potentiates sorafenib to overcome sorafenib-resistant hepatocellular carcinoma |
| title_short | Fucoidan inhibits EGFR redistribution and potentiates sorafenib to overcome sorafenib-resistant hepatocellular carcinoma |
| title_sort | fucoidan inhibits egfr redistribution and potentiates sorafenib to overcome sorafenib resistant hepatocellular carcinoma |
| topic | Fucoidan Sorafenib resistance Hepatocellular carcinoma EGFR |
| url | http://www.sciencedirect.com/science/article/pii/S075333222200991X |
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