Therapeutic Potential of Apatinib Against Colorectal Cancer by Inhibiting VEGFR2-Mediated Angiogenesis and β-Catenin Signaling.

PURPOSE

Apatinib is an inhibitor of VEGFR2 (vascular endothelial growth factor receptor 2) that has attracted a great deal of attention due to its promotion of anticancer activity. In the present study, we investigated the therapeutic effects of apatinib against colorectal cancer (CRC) and examined the underlying mechanism.

MATERIALS AND METHODS

Both in vivo and in vitro assays were conducted to study the effect of apatinib on CRC. To elucidate the associated mechanism, RNA-seq (transcriptome) analysis was conducted on apatinib-treated HCT116 cells.

RESULTS

Apatinib showed antiproliferative and proapoptotic effects, induced G0/G1 arrest and blocked cell migration and invasion in CRC. An analysis of the mechanism associated with apatinib activity demonstrated that by interacting with VEGFR2, apatinib decreased p-Src, p-Akt, and p-GSK3β levels, which further increased β-catenin ubiquitination and reduced the nuclear translocation of β-catenin. Furthermore, apatinib strongly suppressed CT26 cell growth in mouse xenograft models by inhibiting β-catenin signaling and angiogenesis.

CONCLUSION

Overall, the results of the present study here indicated that by inhibiting the VEGFR2-β-catenin-mediated malignant phenotype, apatinib significantly suppresses the growth of CRC, suggesting that the use of apatinib is a promising therapeutic strategy for CRC.