H19-Wnt/beta-catenin regulatory axis mediates the suppressive effects of apigenin on tumor growth in hepatocellular carcinoma
H19-Wnt/beta-catenin regulatory axis mediates the suppressive effects of apigenin on tumor growth in hepatocellular carcinoma
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H19-Wnt/β-连环蛋白调节轴介导芹菜素对肝细胞癌肿瘤生长的抑制作用
DOI：
10.1016/j.ejphar.2020.173810
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发表时间：
2021
影响因子：
5
通讯作者：
Fu Wei-ming
中科院分区：
文献类型：
--
作者：
Pan Fei-fei;Zheng Yan-Biao;Shi Chuan-Jian;Zhang Feng-wei;Zhang Jin-fang;Fu Wei-ming
肝细胞癌（HCC）是世界上癌症相关死亡的主要原因之一。然而，在临床实践中，有效的药理学方法仍然很少。芹菜素（API）是一种具有生物活性的黄酮类化合物，在常见的水果和蔬菜中含量丰富。尽管API的药理活性已被广泛研究，但其在HCC中的生物学功能仍不清楚。在本研究中，我们发现，API强烈抑制肝癌细胞的生长和诱导凋亡。利用异种移植小鼠模型，证明API抑制体内肿瘤生长。已知在HCC中经常升高的长非编码RNA H19在介导肿瘤发生和癌症进展中起重要作用。我们的结果表明，H19被API下调，从而诱导经典的Wnt/β-catenin信号转导的失活。结论：API能够通过H19介导的Wnt/β-catenin信号调节轴抑制肝癌的生长，提示API可能是开发新的肝癌治疗方法的有希望的候选物。
Hepatocellular Carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. However, the effective pharmacological approaches remain scanty in clinical practice. As a bioactive flavonoid, apigenin (API) is enriched in common fruits and vegetables. Although pharmacological activities of API have been widely investigated, its biological function in HCC remains obscure. In the present study, we found that API strongly suppressed cell growth and induced apoptosis in HCC cells. Using a xenograft mice model, API was demonstrated to inhibit thein vivotumor growth. It is known that the long non-coding RNA H19, which is frequently elevated in HCC, plays a vital role in mediating tumorigenesis and cancer progression. Our results demonstrated that H19 was down-regulated by API, and thereby induced the inactivation of the canonical Wnt/β-catenin signaling. In conclusion, our results demonstrated that API was able to suppress tumor growth of HCC through H19-mediated Wnt/β-catenin signaling regulatory axis, suggesting that API may be a promising candidate for developing novel therapeutic approaches against liver cancer.