TY - JOUR AB - Sorafenib, a multi-kinase inhibitor, has shown its promising antitumor effect in a series of clinical trials, and has been approved as the current standard treatment for advanced hepatocellular carcinoma (HCC). 8-Bromo‑7-methoxychrysin (BrMC) is a novel chrysin synthetic analogue that has been reported to inhibit the growth of various tumor cells and possess properties for targeting liver cancer stem cells (LCSCs) . The present study investigated the synergistic targeting effects on the properties of liver cancer stem-like cells (LCSLCs) by a combination of sorafenib and BrMC in SMMC-7721 cell line. We also investigated whether this effect involves regulation of HIF-1α, Twist and NF-κB protein. We found that the sphere-forming cells (SFCs) from the SMMC‑7721 cells possessed the properties of LCSLCs. Sorafenib diminished the self-renewal capacity and downregulated the expression of stem cell biomarkers (CD133, CD44 and ALDH1) in a dose-dependent manner, while BrMC cooperated with sorafenib to strengthen this inhibition. Moreover, the combination of sorafenib and BrMC led to a remarkable decrease in the cellular migration and invasion, the downregulation of N-cadherin protein and upregulation of E-cadherin protein, and increase of cell apoptosis in LCSLCs. BrMC has a remarkable antagonistic effect on the upregulation of protein expression and DNA binding activity of NF-κB (p65) induced by sorafenib. In addition, our results indicated that the synergistic inhibition of sorafenib and BrMC on the characteristics of LCSLCs involves the downregulated expression of HIF-1α and EMT regulator Twist1. Collectively, the combination therapy of sorafenib and BrMC could be a new and promising therapeutic approach in the treatment of HCC. AD - Medical College, Hunan Normal University, Changsha, Hunan 410013, P.R. China School of Pharmaceutical Sciences, and Molecular Imaging Research Center, Central South University, Changsha, Hunan 410013, P.R. China AU - Zou,Hui AU - Cao,Xiaozheng AU - Xiao,Qiao AU - Sheng,Xifeng AU - Ren,Kaiqun AU - Quan,Meifang AU - Song,Zhengwei AU - Li,Duo AU - Zheng,Yu AU - Zeng,Wenbin AU - Cao,Jianguo AU - Peng,Yaojin DA - 2016/09/01 DO - 10.3892/or.2016.4973 EP - 1738 IS - 3 JO - Oncol Rep KW - hepatocellular carcinoma liver cancer stem-like cells 8-bromo-7-methoxychrysin sorafenib synergistic inhibition NF-κB HIF-1α Twist1 PY - 2016 SN - 1021-335X 1791-2431 SP - 1731 ST - Synergistic inhibition of characteristics of liver cancer stem-like cells with a combination of sorafenib and 8-bromo-7-methoxychrysin in SMMC-7721 cell line T2 - Oncology Reports TI - Synergistic inhibition of characteristics of liver cancer stem-like cells with a combination of sorafenib and 8-bromo-7-methoxychrysin in SMMC-7721 cell line UR - https://doi.org/10.3892/or.2016.4973 VL - 36 ER -