Fibrinogen-Like Protein 1 Modulates Sorafenib Resistance in Human Hepatocellular Carcinoma Cells
Despite liver cancer being the second-leading cause of cancer-related death worldwide, few systemic drugs have been approved. Sorafenib, the first FDA-approved systemic drug for unresectable hepatocellular carcinoma (HCC), is limited by resistance. However, the precise mechanisms underlying this phe...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/10/5330 |
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| author | Yeonghoon Son Na-Rae Shin Sung-Ho Kim Su-Cheol Park Hae-June Lee |
| author_facet | Yeonghoon Son Na-Rae Shin Sung-Ho Kim Su-Cheol Park Hae-June Lee |
| author_sort | Yeonghoon Son |
| collection | DOAJ |
| description | Despite liver cancer being the second-leading cause of cancer-related death worldwide, few systemic drugs have been approved. Sorafenib, the first FDA-approved systemic drug for unresectable hepatocellular carcinoma (HCC), is limited by resistance. However, the precise mechanisms underlying this phenomenon are unknown. Since fibrinogen-like 1 (FGL1) is involved in HCC progression and upregulated after anticancer therapy, we investigated its role in regulating sorafenib resistance in HCC. FGL1 expression was assessed in six HCC cell lines (HepG2, Huh7, Hep3B, SNU387, SNU449, and SNU475) using western blotting. Correlations between FGL1 expression and sorafenib resistance were examined by cell viability, colony formation, and flow cytometry assays. FGL1 was knocked-down to confirm its effects on sorafenib resistance. FGL1 expression was higher in HepG2, Huh7, and Hep3B cells than in SNU387, SNU449, and SNU475 cells; high FGL1-expressing HCC cells showed a lower IC<sub>50</sub> and higher sensitivity to sorafenib. In Huh7 and Hep3B cells, FGL1 knockdown significantly increased colony formation by 61% (<i>p</i> = 0.0013) and 99% (<i>p</i> = 0.0002), respectively, compared to that in controls and abolished sorafenib-induced suppression of colony formation, possibly by modulating ERK and autophagy signals. Our findings demonstrate that sorafenib resistance mediated by FGL1 in HCC cells, suggesting FGL1 as a potential sorafenib-resistance biomarker and target for HCC therapy. |
| first_indexed | 2024-03-10T11:17:26Z |
| format | Article |
| id | doaj.art-c3d59709d67c46af9e4adb348de54123 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T11:17:26Z |
| publishDate | 2021-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-c3d59709d67c46af9e4adb348de541232023-11-21T20:21:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012210533010.3390/ijms22105330Fibrinogen-Like Protein 1 Modulates Sorafenib Resistance in Human Hepatocellular Carcinoma CellsYeonghoon Son0Na-Rae Shin1Sung-Ho Kim2Su-Cheol Park3Hae-June Lee4Division of Basic Radiation Bioscience, Korea Institute of Radiological & Medical Sciences, Seoul 01812, KoreaDivision of Basic Radiation Bioscience, Korea Institute of Radiological & Medical Sciences, Seoul 01812, KoreaCollege of Veterinary Medicine, Chonnam National University, Gwangju 61186, KoreaDepartment of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul 01812, KoreaDivision of Basic Radiation Bioscience, Korea Institute of Radiological & Medical Sciences, Seoul 01812, KoreaDespite liver cancer being the second-leading cause of cancer-related death worldwide, few systemic drugs have been approved. Sorafenib, the first FDA-approved systemic drug for unresectable hepatocellular carcinoma (HCC), is limited by resistance. However, the precise mechanisms underlying this phenomenon are unknown. Since fibrinogen-like 1 (FGL1) is involved in HCC progression and upregulated after anticancer therapy, we investigated its role in regulating sorafenib resistance in HCC. FGL1 expression was assessed in six HCC cell lines (HepG2, Huh7, Hep3B, SNU387, SNU449, and SNU475) using western blotting. Correlations between FGL1 expression and sorafenib resistance were examined by cell viability, colony formation, and flow cytometry assays. FGL1 was knocked-down to confirm its effects on sorafenib resistance. FGL1 expression was higher in HepG2, Huh7, and Hep3B cells than in SNU387, SNU449, and SNU475 cells; high FGL1-expressing HCC cells showed a lower IC<sub>50</sub> and higher sensitivity to sorafenib. In Huh7 and Hep3B cells, FGL1 knockdown significantly increased colony formation by 61% (<i>p</i> = 0.0013) and 99% (<i>p</i> = 0.0002), respectively, compared to that in controls and abolished sorafenib-induced suppression of colony formation, possibly by modulating ERK and autophagy signals. Our findings demonstrate that sorafenib resistance mediated by FGL1 in HCC cells, suggesting FGL1 as a potential sorafenib-resistance biomarker and target for HCC therapy.https://www.mdpi.com/1422-0067/22/10/5330hepatocellular carcinomafibrinogen-like protein 1sorafenibresistance |
| spellingShingle | Yeonghoon Son Na-Rae Shin Sung-Ho Kim Su-Cheol Park Hae-June Lee Fibrinogen-Like Protein 1 Modulates Sorafenib Resistance in Human Hepatocellular Carcinoma Cells International Journal of Molecular Sciences hepatocellular carcinoma fibrinogen-like protein 1 sorafenib resistance |
| title | Fibrinogen-Like Protein 1 Modulates Sorafenib Resistance in Human Hepatocellular Carcinoma Cells |
| title_full | Fibrinogen-Like Protein 1 Modulates Sorafenib Resistance in Human Hepatocellular Carcinoma Cells |
| title_fullStr | Fibrinogen-Like Protein 1 Modulates Sorafenib Resistance in Human Hepatocellular Carcinoma Cells |
| title_full_unstemmed | Fibrinogen-Like Protein 1 Modulates Sorafenib Resistance in Human Hepatocellular Carcinoma Cells |
| title_short | Fibrinogen-Like Protein 1 Modulates Sorafenib Resistance in Human Hepatocellular Carcinoma Cells |
| title_sort | fibrinogen like protein 1 modulates sorafenib resistance in human hepatocellular carcinoma cells |
| topic | hepatocellular carcinoma fibrinogen-like protein 1 sorafenib resistance |
| url | https://www.mdpi.com/1422-0067/22/10/5330 |
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