Abstract
As a novel vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, Apatinib has exhibited antitumor effects in a variety of solid tumors. Extracts of Chinese herbal medicines have emerged as a promising alternative option to increase the sensitivity of patients to chemotherapeutics while alleviating side effects. The present study aimed to investigate the effects of Apatinib and the traditional Chinese herb Tripterine on the proliferation, invasion and apoptosis of human hepatoma Hep3B cells. The expression of VEGFR-2 in Hep3B cells was detected by western blotting and immunofluorescence assays. Hep3B cells were then divided into four different groups: Control group, Apatinib group, Tripterine group and Apatinib plus Tripterine group. The proliferation, invasion and apoptosis of these four groups of Hep3B cells were assessed by MTS, wound healing and Transwell assays, and flow cytometry, respectively. Finally, the levels of the proliferation-associated proteins phosphorylated protein kinase B (p-Akt) and phosphorylated extracellular signal-regulated kinase (p-ERK) and the apoptosis-associated proteins cleaved Caspase-3 and B-cell lymphoma-associated X protein (Bax) were detected by western blotting. The proliferation, migration and invasion of Hep3B cells were significantly inhibited by Apatinib and Tripterine, compared with the control group (P<0.01). The inhibitory effect of the combination group was markedly stronger than that of the Apatinib and Tripterine groups. The downregulation of p-Akt and p-ERK induced by Apatinib and Tripterine was further inhibited in the combination group (P<0.05), and the expression levels of Caspase-3 and Bax were also significantly increased in the combination group (P<0.05). The combination of Apatinib and Tripterine significantly inhibited the proliferation, migration and invasion ability and promoted the apoptosis of Hep3B cells by downregulating the expression of p-Akt and p-ERK, and upregulating the expression of Caspase-3 and Bax.