Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells

  • Authors:
    • Minoru Tomizawa
    • Fuminobu Shinozaki
    • Yasufumi Motoyoshi
    • Takao  Sugiyama
    • Shigenori Yamamoto
    • Makoto Sueishi
  • View Affiliations

  • Published online on: August 27, 2014     https://doi.org/10.3892/ol.2014.2484
  • Pages: 2023-2026
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Abstract

Resistance is one limitation of sorafenib in the treatment of hepatocellular carcinoma (HCC). Insulin-like growth factor-1 receptor (IGF-1R) is involved in cancer cell proliferation. To assess the potential synergistic antitumor effects of picropodophyllin (PPP), an IGF-1R inhibitor, HLF and PLC/PRL/5, HCC cells were treated with PPP alone or PPP in combination with sorafenib, a multikinase inhibitor. Normal human umbilical vein endothelial cells (HUVECs) were also used to analyze the antiangiogenic effects of the drugs. HCC cells and HUVECs were cultured on 96‑well plates, and then treated with PPP, with and without the addition of sorafenib. A 3‑(4,5‑dimethylthiazol‑2‑yl)‑5‑(3‑carboxymethoxyphenyl)‑2‑(4‑sulfophenyl)‑2H‑tetrazolium inner salt assay and hematoxylin and eosin staining were then performed 48 h later. The HCC cells were also analyzed using scratch assays and hematoxylin and eosin staining after 48 h. The proliferation of HLF, PLC/PRF/5 and HUVEC cells was suppressed by the combination of 0.2 µM PPP and 3 µM sorafenib more effectively than by 10 µM sorafenib alone. The motility of HLF and PLC/PRF/5 cells was also suppressed to a greater extent with the combination of PPP at 0.2 µM and sorafenib at 3 µM than with sorafenib at 10 µM alone. The cells that had been treated with 0.2 µM PPP and 3 µM sorafenib also exhibited pyknotic nuclei, which is characteristic of apoptosis. In conclusion, PPP enhanced sorafenib‑mediated suppression of proliferation and motility in HCC cells. Therefore, the combination of PPP and sorafenib may exert antitumor and antiangiogenic effects.
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November-2014
Volume 8 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Tomizawa M, Shinozaki F, Motoyoshi Y, Sugiyama T, Yamamoto S and Sueishi M: Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells. Oncol Lett 8: 2023-2026, 2014
APA
Tomizawa, M., Shinozaki, F., Motoyoshi, Y., Sugiyama, T., Yamamoto, S., & Sueishi, M. (2014). Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells. Oncology Letters, 8, 2023-2026. https://doi.org/10.3892/ol.2014.2484
MLA
Tomizawa, M., Shinozaki, F., Motoyoshi, Y., Sugiyama, T., Yamamoto, S., Sueishi, M."Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells". Oncology Letters 8.5 (2014): 2023-2026.
Chicago
Tomizawa, M., Shinozaki, F., Motoyoshi, Y., Sugiyama, T., Yamamoto, S., Sueishi, M."Picropodophyllin and sorafenib synergistically suppress the proliferation and motility of hepatocellular carcinoma cells". Oncology Letters 8, no. 5 (2014): 2023-2026. https://doi.org/10.3892/ol.2014.2484