These authors contributed equally to this work.
Aplasia Ras homologue member I overexpression induces apoptosis through inhibition of survival pathways in human hepatocellular carcinoma cells in culture and in xenograft
Article first published online: 2 JAN 2013
© The Author(s) Journal compilation © 2011 International Federation for Cell Biology
Cell Biology International
Volume 35, Issue 10, pages 1019–1024, October 2011
How to Cite
Pei, X.-H., Yang, Z., Liu, H.-X. and Qiao, S.-S. (2011), Aplasia Ras homologue member I overexpression induces apoptosis through inhibition of survival pathways in human hepatocellular carcinoma cells in culture and in xenograft. Cell Biology International, 35: 1019–1024. doi: 10.1042/CBI20110023
- Issue published online: 2 JAN 2013
- Article first published online: 2 JAN 2013
- Received 8 January 2011/13 February 2011; accepted 12 April 2011
- aplasia Ras homologue member I (ARHI);
- hepatocellular carcinoma;
- nuclear factor κB (NF-κB);
The aim of the present study was to determine the effects of ARHI (aplasia Ras homologue member I; also known as DIRAS3), a member of the Ras superfamily, on HCC (hepatocellular carcinoma) cells and to define the molecular pathways involved. Stable transfection of ARHI into the HCC cell line Hep3B that lacks expression of this gene reduced cell proliferation significantly as compared with the transfection of empty vector (P<0.01). Moreover, the re-expression of ARHI induced significant apoptosis, whereas a few vector transfectants or non-transfected cells displayed apoptosis. Mechanistically, ARHI restoration impeded the activation of both Akt (also called protein kinase B) and NF-κB (nuclear factor κB). In vivo, restoring ARHI also exerted suppressive effects on xenograft tumour growth, which was coupled with increased apoptosis. Together, these results indicate that ARHI has pro-apoptotic effects on HCC cells, which is associated with the inactivation of both Akt and NF-κB survival pathways.