Dihydroartemisinin inhibits EMT induced by platinum-based drugs via Akt–Snail pathway
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Yuan Qin1,2,*, Guang Yang1,*, Meng Li1,2,*, Hui-Juan Liu2,*, Wei-Long Zhong1,2, Xue-Qin Yan1,2, Kai-Liang Qiao1,2, Jia-Huan Yang1,2, Deng-Hui Zhai1,2, Wei Yang2, Shuang Chen2, Hong-Gang Zhou1,2, Tao Sun1,2 and Cheng Yang1,2
1State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China
2Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China
*These authors have contributed equally to this work
Cheng Yang, email: [email protected]
Tao Sun, email: [email protected]
Keywords: dihydroartemisinin, EMT, Akt, Snail
Received: August 25, 2017 Accepted: September 23, 2017 Published: October 10, 2017
Artemisinin and its derivatives exhibit a high activity against a range of cancer cell types both in vitro and in vivo. In clinical practice, platinum-based anti-cancer chemotherapy is widely used to treat tumors. However, a large proportion of patients receiving these treatments will relapse because of metastasis and drug resistance. The purpose of this study is to explore the combinational anti-metastatic effect of platinum-based drugs and dihydroartemisinin (DHA). Both DDP and oxaliplatin (OXA) at low doses could induce epithelial–mesenchymal transition (EMT) in HCC. Meanwhile, co-administration of DHA could enhance DDP and OXA chemosensitivity in HCC and reverse drug resistance. DHA reversed the morphological changes induced by DDP or OXA and reversed the changes in EMT biomarkers induced by DDP and OXA in HCC in vitro and in vivo via AKT–Snail signaling. DHA significantly increased platinum-based drug sensitivity and suppressed EMT induced by platinum-based drugs via AKT–Snail signaling in HCC. DHA is expected to become the new adjuvant for chemotherapy.
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