Research Papers:
Apigenin sensitizes BEL-7402/ADM cells to doxorubicin through inhibiting miR-101/Nrf2 pathway
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Abstract
Ai-Mei Gao1,2,*, Xiao-Yu Zhang3,* and Zun-Ping Ke4
1Department of Pharmacy, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
2Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
3Division of Gastrointestinal Surgery, Department of General Surgery, The Affiliated Huai'an Hospital of Xuzhou Medical University and The Second People's Hospital of Huai'an, Huai'an, China
4Department of Cardiology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China
*These authors have contributed equally to this study and share first authorship
Correspondence to:
Ai-Mei Gao, email: [email protected]
Zun-Ping Ke, email: [email protected]
Keywords: apigenin, microRNA-101, chemo-sensitization, Nrf2, hepatocellular carcinoma
Received: March 23, 2017 Accepted: May 14, 2017 Published: May 30, 2017
ABSTRACT
Chemo-resistance is one of the main obstacle in hepatocellular carcinoma therapy. Apigenin as a natural bioflavonoid has been exhibited anti-cancer properties in various malignant cancers. The aim of this study is to evaluate the potential chemo-sensitization effect of apigenin in doxorubicin-resistant hepatocellular carcinoma cell line BEL-7402/ADM and to investigate its possible mechanism. We found that apigenin significantly reversed doxorubicin sensitivity and induced caspase-dependent apoptosis in BEL-7402/ADM cells. Furthermore, apigenin induced miR-101 expression, and overexpression of miR-101 mimicked the doxorubicin-sensitizing effect of apigenin. Importantly, we showed that miR-101 was able to target the 3′-UTR of Nrf2. The results suggested that apigenin sensitizes BEL-7402/ADM cells to doxorubicin through miR-101/Nrf2 pathway, which furtherly supports apigenin as a potential chemo-sensitizer for hepatocellular carcinoma.
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