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

作者：Chen Wei Lung; Hsieh Chia Ling; Chen Jiann Hwa; Huang Chih Sheng; Chen Wei Ting; Kuo Yu Cheng; Chen Cheng Yu; Hsu Fei Ting^*

来源：Oncology Letters, 2017, 14(3): 3229-3234.

DOI：10.3892/ol.2017.6540

• amentoflavone
• sorafenib
• resistance
• apoptosis
• hepatocellular carcinoma

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-Hepl (SK-Hep1R) cell line was established for the present study: Initially, the differences in sorafenib-induced cytotoxicity and apoptosis between wild-type SK-Hepl 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-Hepl cells following treatment with different concentrations of sorafenib for 24 h. Apoptosis of SK-Hep1R cells was lower than that of SK-Hepl cells following treatment with 20 mu M 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.

• 出版日期2017-9