Anti-neuropilin-1 monoclonal antibody suppresses the migration and invasion of human gastric cancer cells via Akt dephosphorylation.

Abstract

Neuropilin-1 (NRP-1) is involved in a range of physiological and pathological processes, including neuronal cell guidance, cardiovascular development, immunity, angiogenesis and the pathogenesis of cancer. Targeting of NRP-1 is considered to be a potential cancer therapy and a number of approaches have been investigated, including the use of small interfering RNA, peptides, soluble NRP antagonists and monoclonal antibodies. The present study used a novel anti-neuropilin-1 monoclonal antibody (anti-NRP-1 mAb) to investigate its potential anti-tumor effects on human gastric cancer cells in vitro and in vivo, as well as its underlying mechanisms of action. Using an MTT assay, it was observed that anti-NRP-1 mAb (<150 µg/ml) had no effects on the viability of gastric cancer cell line BGC-823, while a Boyden chamber assay indicated that treatment with anti-NRP-1 mAb suppressed the migration and invasion of BGC-823 cells. Western blot analysis also demonstrated that phosphorylation of Akt was reduced in BGC-823 cells treated with anti-NRP-1 mAb. Furthermore, anti-NRP-1 mAb suppressed the growth of gastric cancer xenograft tumors and downregulated the expression of vascular endothelial growth factor proteins within tumors in nude mice. These data indicate the potential effects of anti-NRP-1 mAb on malignant tumors and suggest that inhibition of NRP-1 function with anti-NRP-1 mAb may be a novel therapeutic approach in the treatment of cancer.