SSAO inhibitors suppress hepatocellular tumor growth in mice

Abstract

Vascular adhesion protein-1 (VAP-1) is both an endothelial adhesion molecule involved in leukocytes emigration, and an oxidase belonging to the family of semicarbazide-sensitive amine oxidases (SSAOs). The enzyme activity of VAP-1 plays an important role in the migration of myeloid-derived suppressor cells (MDSCs) into tumor site, and SSAO inhibitors can block the function of VAP-1. The effects of SSAO inhibitors on leukocyte infiltration and tumor progression were evaluated in H22 hepatocellular carcinoma-bearing C57BL/6 mice. Tumor weight and volume were measured after SSAO inhibitor treatment. Then, MDSCs recruitment and neo-angiogenesis were determined using immunostaining. SSAO inhibitors significantly blocked the catalytic activity of VAP-1 in tumor, attenuated tumor progression, and reduced neo-angiogenesis. CD11b(+) and Gr-1(+) MDSCs, which normally infiltrate into tumors, were significantly diminished in tumor-bearing mice treated with SSAO inhibitors. The present study demonstrated that SSAO inhibitors might have an anti-tumor effect on hepatocellular carcinoma by inhibiting recruitment of CD11b(+) and Gr-1(+) cells and hindering angiogenesis, which could be attributed to impairing the catalytic activity of VAP-1.

Keywords: HYD; LJP1207; MAO-A; MAO-B; MDSCs; Myeloid-derived suppressor cells; Neo-angiogenesis; N′-[2-phenyl-allyl]-hydrazine hydrochloride; PBS; SEM; SSAO; SSAO inhibitors; Tumor growth; VAP-1; Vascular adhesion protein-1; hydralazine; monoamine oxidase-A; monoamine oxidase-B; myeloid-derived suppressor cells; phosphate buffer saline; semicarbazide; semicarbazide-sensitive amine oxidase; vascular adhesion protein-1.