Abstract

Sunitinib is an inhibitor of angiogenesis, and CA-4 is being studied in clinical trials as a vascular disrupting agent. Various combinations involving an anti-angiogenic agent and an anti-vascular agent could cause much more effective anti-tumor responses. The present study indicated that the combination of an anti-angiogenic agent (sunitinib) and an anti-vascular agent (CA-4) exerted synergistic anti-proliferative effect against human carcinoma cells including HO-8910, HepG2 and SMMC-7721 in vitro. The enhanced apoptosis induced by sunitinib plus CA-4 was accompanied by greater extent of mitochondrial depolarization, caspases-3 activation and poly ADP-ribose polymerase (PARP) cleavage in HO-8910 cells. Furthermore, the induction of γ-H2AX was observed in sunitinib plus CA-4 treatment group in HO-8910 cells. Together, these data suggested that the combination of sunitinib and CA-4 could produce synergistic anti-tumor effect via DNA damage-induced apoptosis in vitro, and this combination might be a novel and promising therapeutic approach to the treatment of cancer.

Key words: Combretastatin A-4, sunitinib, combination therapy, apoptosis.