Functional characterization of a potent anti-tumor polysaccharide in a mouse model of gastric cancer

Aims: Natural polysaccharides are emerging as a new class of immunomodulatory agents due to their potent immunostimulatory effects and suitable biocompatibility. The aim of this study was to identify potent and selective anticancer activity of a bioactive polysaccharide. Materials and methods: In vitro, viability assay was performed to screen 16 of bioactive polysaccharides in a panel of normal and cancer cell lines. Foci formation, soft agar, BrdU incorporation, cell cycle analyses, and beta-galactosidase staining were performed to validate the screening results. In vivo, both murine gastric cancer syngeneic and a human gastric tumor xenografts models were applied. Tumor histology, immunohistochemical staining, cytokine array and flow cytometry analyses were assayed. Key findings: BSP (bamboo shaving polysaccharides) was identified as the most selective polysaccharide for inhibiting the growth of six gastric cancer cell lines while having no toxic effect on normal gastric mucosal cells. Similarly, BSP had more potent killing effect on a subset of human stomach cancer cells than liver or lung cancer cells. In vivo, BSP significantly inhibited tumor growth and prolonged the survival of mice bearing a gastric tumor; these effects are mediated by tumor cell apoptosis and remodeling of the tumor microenvironment by boosting both immune cell subpopulations and cytokine production in murine gastric cancer syngeneic model. A significant decrease of F4/80-positive tumor-associated macrophages was also observed. Significance: The findings of this study suggest that the potent and selective anti-tumor activity of bioactive polysaccharides such as BSP warrants clinical testing for the treatment of gastric cancer.