Inhibitory effect of bufalin combined with Hedgehog signaling pathway inhibitors on proliferation and invasion and metastasis of liver cancer cells

  • Authors:
    • Xia Sheng
    • Xiaoting Sun
    • Kang Sun
    • Hua Sui
    • Jianmin Qin
    • Qi Li
  • View Affiliations

  • Published online on: August 22, 2016     https://doi.org/10.3892/ijo.2016.3667
  • Pages: 1513-1524
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Abstract

Hepatocellular carcinoma (HCC) is difficult to diagnose early, resulting in only 30% resection rate. HCC is a relatively chemo-resistant tumor, molecular targeted therapy can only benefit approximately 30% patients with liver cancer. Bufalin (Bu) is one of the topoisomerase II inhibitors, many studies have recently focused on the anticancer activities of bufalin. In the present study, we report that bufalin can inhibit the proliferation, invasion and metastasis of liver cancer cells via the Hh signaling pathway. The human high metastasis potential LM3 hepatoma cells (HCC-LM3) were cultured in vitro, bufalin and/or Hedgehog signaling pathway inhibitors (GANT61, cyclopamine) was added into cell culture fluid for 72 h to observe the antitumor effect of bufalin. The results showed that bufalin was able to inhibit epithelial mesenchymal transition (EMT), and extracellular matrix (ECM) degradation and angiogenesis of liver cancer cells by influencing the expression of Ptch1'Gli1'Gli3 proteins in Hh signaling pathway. Bufalin could downregulate the downstream target molecules of MMP-2, MMP-9, β-catenin and VEGF in liver cancer cells by influencing the Gli1 and Gli3 expression of Hh signaling pathway, and upregulate the E-cadherin expression of liver cancer cells by influencing the Gli3 expression of Hh signaling pathway. Therefore, the present study shows that bufalin combined with Hedgehog signaling pathway inhibitors can significantly reduce the malignant biological behavior of the liver cancer cells.
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October-2016
Volume 49 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Sheng X, Sun X, Sun K, Sui H, Qin J and Li Q: Inhibitory effect of bufalin combined with Hedgehog signaling pathway inhibitors on proliferation and invasion and metastasis of liver cancer cells . Int J Oncol 49: 1513-1524, 2016
APA
Sheng, X., Sun, X., Sun, K., Sui, H., Qin, J., & Li, Q. (2016). Inhibitory effect of bufalin combined with Hedgehog signaling pathway inhibitors on proliferation and invasion and metastasis of liver cancer cells . International Journal of Oncology, 49, 1513-1524. https://doi.org/10.3892/ijo.2016.3667
MLA
Sheng, X., Sun, X., Sun, K., Sui, H., Qin, J., Li, Q."Inhibitory effect of bufalin combined with Hedgehog signaling pathway inhibitors on proliferation and invasion and metastasis of liver cancer cells ". International Journal of Oncology 49.4 (2016): 1513-1524.
Chicago
Sheng, X., Sun, X., Sun, K., Sui, H., Qin, J., Li, Q."Inhibitory effect of bufalin combined with Hedgehog signaling pathway inhibitors on proliferation and invasion and metastasis of liver cancer cells ". International Journal of Oncology 49, no. 4 (2016): 1513-1524. https://doi.org/10.3892/ijo.2016.3667