The suppressing effects of VEGF-mediated angiogenesis at different administration sequences of apatinib and transarterial embolization in vivo

BACKGROUND: To investigate the suppressing effects of vascular endothelial growth factor (VEGF)-mediated angiogenesis at different treatment schedules by applying apatinib combined with transarterial embolization (TAE). METHODS: Forty ideal liver cancer rat models were randomly divided into four groups based on different administration methods of apatinib [control group (CG): TAE only; Combined Group 1 (CG1): apatinib administration 3 days pre-TAE; Combined Group 2 (CG2): apatinib administration simultaneously with TAE; Combined Group 3 (CG3): apatinib administration 3 days post-TAE]. The characteristics of liver cancer, the expression of VEGF and microvascular density (MVD) as determined by CD34, and the overall survival (OS) were compared among the groups. RESULTS: The tumor sizes of the liver on the 10th day after treatment were significantly larger when compared to the baseline sizes (P<0.05), and tumor growth in the combined groups was significantly slower than that of CG (P<0.05). The OS of rats was significantly different between the combined groups and control group (P<0.05), which were 19.9±3.21, 31.2±6.48, 27.1±5.59, and 25.9±6.06 days in groups CG, CG1, CG2 and CG3, respectively. Significant differences were observed between groups CG1 and CG3. The expression levels of VEGF in groups CG1, CG2 and CG3 were 45.6±9.88, 70.8±14.11 and 75.3±9.82, and were significantly lower than that in control groups (85.8±11.26). The MVD in CG (109.7±10.32) reached the peak value when compared to those in the three combined groups (46.4±19.22, 75.7±15.97, and 90.5±12.71, all P<0.05). Furthermore, overexpression of VEGF and MVD showed significant positive correlation with poor OS. CONCLUSIONS: These findings demonstrated that apatinib treatment enhanced anti-tumor effects of TAE via reducing tumor angiogenesis, suppressing tumor growth, and prolonging the OS of rats with liver tumors. Early administration of apatinib showed better therapeutic effects.