Amentoflavone enhances sorafenib‑induced apoptosis through extrinsic and intrinsic pathways in sorafenib‑resistant hepatocellular carcinoma SK‑Hep1 cells in vitro

Chen,Wei‑Lung; Hsieh,Chia‑Ling; Chen,Jiann‑Hwa; Huang,Chih‑Sheng; Chen,Wei‑Ting; Kuo,Yu‑Cheng; Chen,Cheng‑Yu; Hsu,Fei‑Ting

doi:10.3892/ol.2017.6540

Amentoflavone enhances sorafenib‑induced apoptosis through extrinsic and intrinsic pathways in sorafenib‑resistant hepatocellular carcinoma SK‑Hep1 cells in vitro

Authors:
- Wei‑Lung Chen
- Chia‑Ling Hsieh
- Jiann‑Hwa Chen
- Chih‑Sheng Huang
- Wei‑Ting Chen
- Yu‑Cheng Kuo
- Cheng‑Yu Chen
- Fei‑Ting Hsu
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Affiliations: Department of Emergency Medicine, Cathay General Hospital, Taipei 106, Taiwan, R.O.C., The Ph.D. Program for Translational Medicine College of Medical Science and Technology, Taipei Medical University, Taipei 110, Taiwan, R.O.C., Division of Colon and Rectal Surgery, Department of Surgery, National Yang‑Ming University Hospital, Yilan 260, Taiwan, R.O.C., Department of Psychiatry, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 813, Taiwan, R.O.C., Radiation Oncology, Show Chwan Memorial Hospital, Changhua 500, Taiwan, R.O.C., Department of Medical Imaging, Taipei Medical University Hospital, Taipei 110, Taiwan, R.O.C.
Published online on: July 8, 2017 https://doi.org/10.3892/ol.2017.6540
Pages: 3229-3234

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Abstract

The present study aimed to evaluate the effects of amentoflavone on sorafenib‑induced apoptosis in sorafenib‑resistant hepatocellular carcinoma (HCC) cells. The sorafenib‑resistant SK‑Hep1 (SK‑Hep1R) cell line was established for the present study. Initially, the differences in sorafenib‑induced cytotoxicity and apoptosis between wild‑type SK‑Hep1 and SK‑Hep1R cells were verified using the MTT assay and flow cytometry. The effects of amentoflavone on sorafenib‑induced cytotoxicity and apoptosis were then investigated using MTT, flow cytometry, DNA gel electrophoresis and western blot analysis. The results demonstrated that cell viability of SK‑Hep1R cells was increased compared with that of SK‑Hep1 cells following treatment with different concentrations of sorafenib for 24 h. Apoptosis of SK‑Hep1R cells was lower than that of SK‑Hep1 cells following treatment with 20 µM sorafenib for 24 h. Amentoflavone alone did not inhibit cell viability but significantly triggered sorafenib‑induced cytotoxicity and apoptosis in SK‑Hep1R cells. Amentoflavone not only reversed sorafenib‑induced anti‑apoptotic protein levels but also enhanced sorafenib‑induced pro‑apoptotic protein expression in SK‑Hep1R cells. In conclusion, amentoflavone may be used as a sorafenib sensitizer to enhance sorafenib‑induced cytotoxicity and trigger sorafenib‑induced apoptosis through extrinsic and intrinsic pathways in SK‑Hep1R cells.

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