Dihydroartemisinin inhibits the migration of esophageal cancer cells by inducing autophagy
Dihydroartemisinin inhibits the migration of esophageal cancer cells by inducing autophagy
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DOI：
10.3892/ol.2020.11955
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发表时间：
2020-10-01
期刊：
影响因子：
2.9
通讯作者：
He, Yao
中科院分区：
文献类型：
--
作者：
Chen, Xiao;He, Lan-Ying;He, Yao
食管癌是一种复杂的胃肠道恶性肿瘤，全球发病率居所有癌症类型的第7位。由于其侵袭性和早期转移的可能性，EC患者的生存率很低。双氢青蒿素（DHA）是青蒿素的主要活性衍生物，并且除了其作为抗疟疾的用途之外，DHA还在各种癌症模型中表现出抗肿瘤活性，例如胆管癌、头颈癌和肝细胞癌细胞。然而，DHA在EC治疗中的抗肿瘤作用的分子机制仍然知之甚少。本研究的结果表明，DHA通过激活自噬以剂量依赖的方式显著抑制TE-1和Eca-109 EC细胞的迁移。DHA治疗还通过下调上皮-间质转化（EMT）相关标志物N-钙粘蛋白和波形蛋白以及上调E-钙粘蛋白的表达来显著逆转EMT。从机制上讲，DHA治疗降低了Akt磷酸化并抑制了Akt/mTOR信号通路，导致自噬的激活。当Akt的活性形式过表达时，自噬相关蛋白的水平被抑制，并且DHA介导的对EC细胞迁移的抑制被逆转。总之，本研究证明了DHA在治疗EC中的潜在价值，并揭示了FDHA抑制细胞迁移的潜在机制。
Esophageal cancer (EC) is a complex gastrointestinal malignancy and its global incidence rate ranks 7th among all cancer types. Due to its aggressive nature and the potential for early metastasis, the survival rates of patients with EC are poor. Dihydroartemisinin (DHA) is the primary active derivative of artemisinin, and, as well as its use as an anti-malarial, DHA has also exhibited antitumor activity in various cancer models, such as cholangiocarcinoma, head and neck carcinoma, and hepatocellular carcinoma cells. However, the molecular mechanisms underlying the antitumor effect of DHA in the treatment of EC remains poorly understood. The results of the present study demonstrated that DHA significantly inhibited the migration of TE-1 and Eca-109 EC cells in a dose-dependent manner by activating autophagy. DHA treatment also significantly reversed epithelial-mesenchymal transition (EMT) by downregulating the EMT-associated markers, N-cadherin and vimentin, and upregulating the expression of E-cadherin. Mechanistically, DHA treatment decreased Akt phosphorylation and inhibited the Akt/mTOR signaling pathway, leading to the activation of autophagy. The levels of the autophagy-associated proteins were suppressed and DHA-mediated inhibition of migration in EC cells was reversed when an active form of Akt was overexpressed. In conclusion, the present study demonstrated the potential value of DHA in the treatment of EC, and revealed the underlying mechanism by which FDHA inhibits cellular migration.