Atractylenolide III predisposes miR‐195‐5p/FGFR1 signaling axis to exert tumor‐suppressive functions in liver cancer

Background Antineoplastic activity of atractylenolide III (ATL) has been reported in several malignant tumors. However, its activity has not been completely clarified in hepatocellular carcinoma (HCC). Herein, anticancer effects and underlying molecular mechanisms of ATL were investigated in HCC cel...

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Published in:Journal of food biochemistry 2021-05, Vol.45 (5), p.e13582-n/a
Main Authors: Sheng, Langqing, Li, Jiarong, Li, Nianfeng, Gong, Liansheng, Liu, Ling, Zhang, Qi, Li, Xiaoli, Luo, Hui, Chen, Zeguo
Format: Article
Language:English
Subjects:
apoptosis
atractylenolide III
Carcinoma, Hepatocellular - drug therapy
Carcinoma, Hepatocellular - genetics
Cell Line, Tumor
FGFR1
Gene Expression Regulation, Neoplastic
Hep G2 Cells
hepatocellular carcinoma
Humans
Lactones
Liver Neoplasms - drug therapy
Liver Neoplasms - genetics
MicroRNAs - genetics
migration
Receptor, Fibroblast Growth Factor, Type 1 - genetics
Sesquiterpenes
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Summary:Background Antineoplastic activity of atractylenolide III (ATL) has been reported in several malignant tumors. However, its activity has not been completely clarified in hepatocellular carcinoma (HCC). Herein, anticancer effects and underlying molecular mechanisms of ATL were investigated in HCC cells in vitro. Methods Cell viability was evaluated by CCK‐8 assay. Cell migration and invasion were evaluated using the transwell assay. TUNEL staining was performed to evaluate cell apoptosis. Protein expression was measured by western blotting analysis. Online database TargetScan and luciferase reporter gene analysis were performed to validate FGFR1 as a target of miR‐195‐5p. Results HepG2 and SMMC7721 cell growth, migration, and invasion were inhibited by ATL treatment in a dose‐dependent pattern. ATL treatment‐induced apoptosis of HepG2 and SMMC7721 cells. Intriguingly, ATL treatment unexpectedly inhibited FGFR1 protein expression in HepG2 and SMMC7721 cells. Knockdown of FGFR1 inhibited proliferation, migration, and invasion, and evoked apoptosis of HepG2 and SMMC7721 cells. We also found that ATL treatment could increase the expression of miR‐195‐5p, which as a posttranscriptional targeted FGFR1. In HCC tissues, miR‐195‐5p expression is negatively correlated with FGFR1. Furthermore, the antiproliferative and proapoptotic roles of miR‐195‐5p were neutralized by overexpressed FGFR1 in HCC cells. Conclusion ATL effectively repressed growth and induced apoptosis of human HCC cells through the upregulation of miR‐195‐5p to downregulate FGFR1 expression. Practical applications Atractylenolide III as a bioactive anticancer adjuvant medication will provide chemosensitization strategy for reversing the drug resistance of HCC. Atractylenolide III mediates miR‐195‐5p/FGFR1 signaling axis to exert tumor‐suppressive functions in liver cancer. Atractylenolide III may be a prospective anticancer adjuvant medication to improve drug resistance of HCC.
ISSN:0145-8884
1745-4514
DOI:10.1111/jfbc.13582