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

  • Authors:
    • Hui Zou
    • Xiaozheng Cao
    • Qiao Xiao
    • Xifeng Sheng
    • Kaiqun Ren
    • Meifang Quan
    • Zhengwei Song
    • Duo Li
    • Yu Zheng
    • Wenbin Zeng
    • Jianguo Cao
    • Yaojin Peng
  • View Affiliations

  • Published online on: July 25, 2016     https://doi.org/10.3892/or.2016.4973
  • Pages: 1731-1738
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

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.
View Figures
View References

Related Articles

Journal Cover

September-2016
Volume 36 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Zou H, Cao X, Xiao Q, Sheng X, Ren K, Quan M, Song Z, Li D, Zheng Y, Zeng W, Zeng W, et al: 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. Oncol Rep 36: 1731-1738, 2016.
APA
Zou, H., Cao, X., Xiao, Q., Sheng, X., Ren, K., Quan, M. ... Peng, Y. (2016). 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. Oncology Reports, 36, 1731-1738. https://doi.org/10.3892/or.2016.4973
MLA
Zou, H., Cao, X., Xiao, Q., Sheng, X., Ren, K., Quan, M., Song, Z., Li, D., Zheng, Y., Zeng, W., Cao, J., Peng, Y."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". Oncology Reports 36.3 (2016): 1731-1738.
Chicago
Zou, H., Cao, X., Xiao, Q., Sheng, X., Ren, K., Quan, M., Song, Z., Li, D., Zheng, Y., Zeng, W., Cao, J., Peng, Y."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". Oncology Reports 36, no. 3 (2016): 1731-1738. https://doi.org/10.3892/or.2016.4973