Effective inhibition of xenografts of hepatocellular carcinoma (HepG2) by rapamycin and bevacizumab in an intrahepatic model.
OBJECTIVE
Hepatocellular carcinoma (HCC) displays a characteristic hypervascularity and depends on angiogenesis for tumor growth, which thus provides a potential target for therapeutic approaches to HCC. In this study, through the use of combined micro-positron emission tomography (PET)/computed tomography (CT), we investigate if such a combined targeting of vascular endothelial growth factor (VEGF) activity and expression might retard HCC growth in an orthotopic intrahepatic xenograft model.


METHODS
Xenograft models were created by intraportal vein injection of HepG2 cell suspensions in severe combined immunodeficient mice. The mice were then treated with (1) rapamycin (RAPA), a mammalian target of rapamycin pathway inhibitor; (2) bevazicumab (BEV), a VEGF monoclonal antibody; and (3) a RAPA/BEV combination.


RESULTS
Assessment of HCC progression using CT with Omnipaque and PET with 2-deoxy-2-(F-18)-fluoro-D: -glucose showed that mice treated with RAPA/BEV had the lowest standardized uptake values (SUVs). At week 2, mice treated with RAPA/BEV, RAPA, and BEV all showed a marked decrease in the SUV(max) readings with the greatest drop being observed in the RAPA/BEV group (1.33 + 0.26, 1.81 + 0.2, 2.05 + 0.4 vs. vehicle control 2.11 + 0.53).


CONCLUSIONS
Our results, supported by micro-PET/CT, suggest that RAPA/BEV represents a potential novel antiangiogenic therapy for the treatment of HCC.
Ong
Lai-Chun
LC
Singapore General Hospital, Outram Road, Singapore, 169608, Singapore.
Song
In-Chin
IC
Jin
Yi
Y
Kee
Irene H C
IH
Siew
Eeyan
E
Yu
Sidney
S
Thng
Choon-Hua
CH
Huynh
Hung
H
Chow
Pierce K H
PK