The Antitumor Potential of λ-Carrageenan Oligosaccharides on Gastric Carcinoma by Immunomodulation

Abstract

Gastric carcinoma is a frequently detected malignancy worldwide, while its mainstream drugs usually result in some adverse reactions, including immunosuppression. λ-carrageenan oligosaccharides (COS) have attracted increasing attention as potential anticancer agents due to their ability to enhance immune function. Our current work assessed the antitumor mechanism of λ-COS using BGC-823 cells. Our findings indicated that λ-COS alone did not have a significant impact on BGC-823 cells in vitro; however, it was effective in inhibiting tumor growth in vivo. When THP-1 cells were pre-incubated with λ-COS and used to condition the medium, BGC-823 cells in vitro displayed a concentration-dependent induction of cell apoptosis, nuclear damage, and the collapse of mitochondrial transmembrane potential. These findings suggested that the antineoplastic effect of λ-COS was primarily due to its immunoenhancement property. Treatment with λ-COS was found to significantly enhance the phagocytic capability of macrophages, increase the secretion of TNF-α and IFN-γ, and improve the indexes of spleen and thymus in BALB/c mice. In addition, λ-COS was found to inhibit the growth of BGC-823-derived tumors in vitro by activating the Par-4 signaling pathway, which may be stimulated by the combination of TNF-α and IFN-γ. When used in combination with 5-FU, λ-COS demonstrated enhanced anti-gastric carcinoma activity and improved the immunosuppression induced by 5-FU alone. These findings suggested that λ-COS could be used as an immune-modulating agent for chemotherapy.