Abstract
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. 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. 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. ATL effectively repressed growth and induced apoptosis of human HCC cells through the upregulation of miR-195-5p to downregulate FGFR1 expression. Atractylenolide III as a bioactive anticancer adjuvant medication will provide chemosensitization strategy for reversing the drug resistance of HCC.
Highlights
Hepatocellular carcinoma (HCC) is the most common cause of global cancer-associated mortality with a 1-year survival rate of less than 50% [1]
The results demonstrated that the cell viability of MHCC97H (Figure 1B), HepG2 (Figure 1C), Huh7 (Figure 1D) and SMMC7721 (Figure 1E) were inhibited by atractylenolide III (ATL) treatment in a dose-dependent manner
We revealed that 7 miRNAs, including miR-935p, miR-214-3p, miR-199a-5p, miR-195-5p, miR-150-5p, miR-145-5p and miR-130a-3p, had the complementary sequence in the 3’-untranslated region (3’-UTR) of fibroblast growth factor receptor1 (FGFR1) messenger RNA (mRNA)
Summary
Hepatocellular carcinoma (HCC) is the most common cause of global cancer-associated mortality with a 1-year survival rate of less than 50% [1]. Palliative chemotherapy, including doxorubicin, mitomycin, cisplatin and 5-fluorouracil, is the main method for treatment and improves survival among patients with HCC [3,4,5]. New treatment strategies are significant for improving therapeutic effects for patients with HCC. Atractylenolide III (ATL) is a sesquiterpenoid and is the major active ingredient of Atractylodes macrocephala Koidz [8], and is found in a range of other medical herbs, such as Codonopsis pilosula, Chloranthus henryi Hemsl and Atractylodes lancea. Antineoplastic activity of atractylenolide III (ATL) has been reported in several malignant tumors. Its activity has not been completely clarified in hepatocellular carcinoma (HCC). Anti-cancer effects and underlying molecular mechanisms of ATL were investigated in HCC cells in vitro
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