Although
apatinib has been demonstrated with potential antitumor activity in multiple solid
tumors, the underlying mechanism of
apatinib for the treatment of
hepatocellular carcinoma (HCC) remains unclear. In the present study, we explored if there are any direct suppression effects of
apatinib on HCC cells and its relevant targets. We investigated the effect of
apatinib on viability of five HCC cell lines and an
intrahepatic cholangiocarcinoma cell line, and colony formation, apoptosis and migration of representative HCC cells in vitro; and HCC progression in a xenograft mouse model. Using a phospho-
receptor tyrosine kinase pathway array with 49 different
tyrosine kinases, we screened and verified the
tyrosine kinase targets involved in
apatinib response.
Apatinib treatment significantly inhibited HCC cell viability, proliferation, colony formation, and migration, and enhanced cell apoptosis in a concentration-dependent manner (p < 0.05). Furthermore,
apatinib showed a favorable anti-
tumor growth effect (71% of inhibition ratio, p < 0.05) in an established human HCC xenograft mice model with good safety. RTK pathway arrays and western blots analysis demonstrated that
apatinib significantly downregulated the phosphorylation levels of several
tyrosine kinase receptors, particularly PDGFR-α and IGF-IR, and inhibited Akt phosphorylation. These data suggest that the
apatinib may have a direct anti-HCC effect as a direct multi-target RTK inhibitor of HCC cells and a promising potentiality in HCC clinical
therapies.