Journal
ONCOTARGET
Volume 8, Issue 47, Pages 82085-82091Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.18294
Keywords
apigenin; microRNA-101; chemo-sensitization; Nrf2; hepatocellular carcinoma
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Funding
- Yangfan Project of Shanghai Science and Technology Commission [14YF1411900]
- National Natural Science Foundation of China [81402949]
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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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