Department of Hepatobiliary and Pancreatic Surgery, Xiangya Hospital of Central South University, Changsha, China.
J Food Biochem. 2021 May;45(5):e13582. doi: 10.1111/jfbc.13582. Epub 2021 Mar 26.
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.
几种恶性肿瘤已报道有苍术内酯 III（ATL）的抗肿瘤活性。然而，其在肝细胞癌（HCC）中的活性尚未完全阐明。在此，我们研究了 ATL 在体外 HCC 细胞中的抗癌作用及其潜在的分子机制。
通过 CCK-8 法评估细胞活力。使用 Transwell 测定法评估细胞迁移和侵袭。通过 TUNEL 染色评估细胞凋亡。通过 Western blot 分析测量蛋白表达。在线数据库 TargetScan 和荧光素酶报告基因分析用于验证 FGFR1 是 miR-195-5p 的靶标。
HepG2 和 SMMC7721 细胞的生长、迁移和侵袭均被 ATL 处理以剂量依赖的方式抑制。ATL 处理诱导 HepG2 和 SMMC7721 细胞凋亡。有趣的是，ATL 处理出人意料地抑制了 HepG2 和 SMMC7721 细胞中的 FGFR1 蛋白表达。FGFR1 的敲低抑制了 HepG2 和 SMMC7721 细胞的增殖、迁移和侵袭，并引发了细胞凋亡。我们还发现 ATL 处理可以增加 miR-195-5p 的表达，miR-195-5p 作为 FGFR1 的转录后靶向物。在 HCC 组织中，miR-195-5p 的表达与 FGFR1 呈负相关。此外，在 HCC 细胞中过表达 FGFR1 可中和 miR-195-5p 的抗增殖和促凋亡作用。
ATL 通过上调 miR-195-5p 下调 FGFR1 表达，有效抑制人 HCC 细胞的生长并诱导细胞凋亡。
苍术内酯 III 作为一种生物活性抗癌辅助药物，将为逆转 HCC 的药物耐药性提供化学增敏策略。
