Fibrinogen-like protein 1 modulates sorafenib resistance in human hepatocellular carcinoma cells

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Title
Fibrinogen-like protein 1 modulates sorafenib resistance in human hepatocellular carcinoma cells
Author(s)
Yeonghoon Son; N R Shin; S H Kim; S C Park; H J Lee
Bibliographic Citation
International Journal of Molecular Sciences, vol. 22, no. 10, pp. 5330-5330
Publication Year
2021
Abstract
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 IC50 and higher sensitivity to sorafenib. In Huh7 and Hep3B cells, FGL1 knockdown significantly increased colony formation by 61% (p = 0.0013) and 99% (p = 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.
Keyword
Hepatocellular carcinomaFibrinogen-like protein 1SorafenibResistance
ISSN
1661-6596
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/ijms22105330
Type
Article
Appears in Collections:
Jeonbuk Branch Institute > Primate Resources Center > 1. Journal Articles
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