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- Title
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
- 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-carbo xymethoxyphenyl)-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.
- Subjects
LIVER cancer; VASCULAR endothelial growth factors; CANCER cells; SOMATOMEDIN C; SOMATOMEDIN
- Publication
Oncology Letters, 2014, Vol 8, Issue 5, p2023
- ISSN
1792-1074
- Publication type
Article
- DOI
10.3892/ol.2014.2484