Hepatocellular carcinoma (HCC) is the third-leading cause of
cancer-related deaths with 750,000 newly diagnosed cases each year. Surgery,
radiotherapy, and
chemotherapy constitute the main treatment modalities for HCC, but
liver cirrhosis and damage often occur. Molecular targeted drugs have been recently developed to treat HCC.
Vascular endothelial growth factor (
VEGF)/
VEGF receptor (VEGFR) autocrine signaling is closely related to the growth, progression, and
metastasis of HCC, making the
VEGF/VEGFR axis an ideal target for the development of molecular targeted agents. Here, we report the effects of the novel anti-
VEGF humanized
monoclonal antibody BD0801 on the growth of HCC cells in vitro and in vivo as well as the underlying mechanisms. BD0801 significantly inhibited the proliferation of HepG2, SMMC-7721, and Bel7402 cells in vitro, accompanied with an induction of apoptosis and cell cycle arrest at the G1 phase. BD0801 potently suppressed AKT, Erk1/2, and
retinoblastoma (Rb) phosphorylation, while increasing p21 and decreasing
cyclin D1 protein levels. BD0801 significantly inhibited growth in mouse
tumor xenografts and induced cell apoptosis of HepG2 and SMMC-7721
tumor xenografts. Furthermore, BD0801 effectively reduced the vascular density and
tumor tissue microvessel density (MVD). Similarly, BD0801 decreased AKT, Erk1/2, and Rb phosphorylation and
cyclin D1 expression whereas it increased p21
protein expression in mouse HCC
tumor xenografts. Importantly, BD0801 showed a better effect than
Bevacizumab (Bev) on the inhibition of cell growth and induction of apoptosis in HCC cells in vitro and in vivo. These findings suggest that BD0801 is a potent anti-
VEGF monoclonal antibody for the treatment of HCC.