The objective of this study is to investigate antiproliferative activities against
gastric cancer and anti-angiogenesis of DCT015, a novel
sorafenib derivate, and potential mechanisms. The effects of DCT015 on proliferation and apoptosis in
gastric cancer cells were evaluated by cytotoxicity assays, apoptosis analysis, flow cytometry analysis, and Western blotting assays. The in vivo antitumor effects were carried out in nude mice bearing
gastric cancer. On the other hand, the
anti-angiogenesis effects of DCT015 were measured by human umbilical vein endothelial cell (HUVEC) proliferation, migration, tube formation, and Western blotting analysis. The results showed that DCT015 inhibited the proliferation, induced the morphological changes of apoptosis, and increased the apoptosis percentage, as well as increased the "sub-G1" population in
gastric cancer cells. DCT015 also significantly decreased the
tumor volumes and
tumor weights in vivo by
oral administration. Immunohistochemistry assay demonstrated that DCT015 inhibited
tumor growth and neovascularization. In vitro studies found that DCT015 inhibited both
MEK/ERK and PI3K/Akt signaling pathways by Western blotting assays. Moreover, DCT015 significantly inhibited
VEGF-induced migration and tube formation in HUVECs. Western blotting analysis showed that DCT015 downregulated
VEGF-induced VEGFR2 phosphorylation with the decreased phosphorylation of the downstream key
proteins. Taken together, our findings highlight that DCT015 is a promising orally anticancer drug for treating
gastric cancer.