Research Papers:

Apigenin sensitizes BEL-7402/ADM cells to doxorubicin through inhibiting miR-101/Nrf2 pathway

Ai-Mei Gao _, Xiao-Yu Zhang and Zun-Ping Ke

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Oncotarget. 2017; 8:82085-82091. https://doi.org/10.18632/oncotarget.18294

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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


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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