Qin Yuan, Yang Guang, Li Meng, Liu Hui-Juan, Zhong Wei-Long, Yan Xue-Qin, Qiao Kai-Liang, Yang Jia-Huan, Zhai Deng-Hui, Yang Wei, Chen Shuang, Zhou Hong-Gang, Sun Tao, Yang Cheng
State Key Laboratory of Medicinal Chemical Biology and College of Pharmacy, Nankai University, Tianjin, China.
Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin, China.
Oncotarget. 2017 Oct 10;8(61):103815-103827. doi: 10.18632/oncotarget.21793. eCollection 2017 Nov 28.
Artemisinin and its derivatives exhibit a high activity against a range of cancer cell types both and . 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 and 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.
青蒿素及其衍生物对多种癌细胞类型均表现出高活性。在临床实践中，铂类抗癌化疗被广泛用于治疗肿瘤。然而，接受这些治疗的很大一部分患者会因转移和耐药性而复发。本研究的目的是探索铂类药物与双氢青蒿素（DHA）的联合抗转移作用。低剂量的顺铂（DDP）和奥沙利铂（OXA）均可诱导肝癌细胞发生上皮-间质转化（EMT）。同时，联合使用DHA可增强肝癌细胞对DDP和OXA的化疗敏感性并逆转耐药性。DHA通过AKT-Snail信号通路逆转了DDP或OXA诱导的形态学变化以及DDP和OXA在肝癌细胞中诱导的EMT生物标志物变化。DHA通过AKT-Snail信号通路显著提高了铂类药物敏感性并抑制了铂类药物诱导的肝癌细胞EMT。DHA有望成为新的化疗辅助药物。
