Brian Irving Carr, Aldo Cavallini, Catia Lippolis, Rosalba D'Alessandro, Caterina Messa, and Maria Grazia Refolo contributed equally to this work.
Original Research Article
Article first published online: 25 FEB 2013
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 228, Issue 6, pages 1344–1350, June 2013
How to Cite
Carr, B. I., D'Alessandro, R., Refolo, M. G., Iacovazzi, P. A., Lippolis, C., Messa, C., Cavallini, A., Correale, M. and Di Carlo, A. (2013), Effects of low concentrations of Regorafenib and Sorafenib on human HCC cell AFP, migration, invasion, and growth in vitro. J. Cell. Physiol., 228: 1344–1350. doi: 10.1002/jcp.24291
Conflict of interest: none.
- Issue published online: 25 FEB 2013
- Article first published online: 25 FEB 2013
- Accepted manuscript online: 20 NOV 2012 09:04AM EST
- Manuscript Accepted: 13 NOV 2012
- Manuscript Received: 20 JUL 2012
- NIH support. Grant Number: CA82723-09
Sorafenib was shown in clinical trial to enhance survival in hepatocellular carcinoma (HCC) patients, but with minimal tumor shrinkage. To correlate several indices of HCC growth at various drug concentrations, HCC cells were grown in various low concentrations of two multikinase inhibitors, Regorafenib (Stivarga) and Sorafenib (Nexavar) and their effects were examined on alpha-fetoprotein (AFP), cell growth, migration, and invasion. In two AFP positive human HCC cell lines, AFP was inhibited at 0.1–1 µM drug concentrations. Cell migration and invasion were also inhibited at similar low drug concentrations. However, 10-fold higher drug concentrations were required to inhibit cell growth in both AFP positive and negative cells. To investigate this concentration discrepancy of effects, cells were then grown for prolonged times and sub-cultured in low drug concentrations and then their growth was re-tested. The growth in these drug-exposed cells was found to be slower than cells without prior drug exposure and they were also more sensitive to subsequent drug challenge. Evidence was also found for changes in cell signaling pathways in these slow-growth cells. Low multikinase inhibitor concentrations thus modulate several aspects of HCC cell biology. J. Cell. Physiol. 228: 1344–1350, 2013. © 2012 Wiley Periodicals, Inc.