Aplasia Ras homologue member I overexpression induces apoptosis through inhibition of survival pathways in human hepatocellular carcinoma cells in culture and in xenograft.

Abstract:

: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.

journal_name

Cell Biol Int

authors

Pei XH,Yang Z,Liu HX,Qiao SS

doi

10.1042/CBI20110023

subject

Has Abstract

pub_date

2011-10-01 00:00:00

pages

1019-24

issue

10

eissn

1065-6995

issn

1095-8355

pii

CBI20110023

journal_volume

35

pub_type

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