Background/AimsGrowing evidence supports the direct link of Fusobacterium nucleatum with colorectal cancer (CRC). However, to date, the underlying mechanism of action remains poorly understood. In this study, we examined the effects of F. nucleatum on the progression of CRC and investigated whether cyclin-dependent kinase 5 (Cdk5) is involved in the effect through activating the Wnt/β-catenin signaling pathway.Materials and MethodsCRC tissues and matched histologically normal specimens were collected from patients who were diagnosed with CRC and underwent surgical treatment in our hospital between January 2018 and January 2019. Two human CRC cell lines, including DLD-1 and SW480, were utilized mainly for in vitro mechanistic investigations.ResultsThe abundance of F. nucleatum was significantly greater in CRC tissues than in cancer-free specimens, which was significantly correlated with the progression of CRC. In vitro investigations revealed that F. nucleatum significantly enhanced the proliferation and migration of CRC cells. Furthermore, F. nucleatum significantly induced the expression of Cdk5 and activation of the Wnt/β-catenin signaling pathway. Notably, knockdown of Cdk5 significantly abrogated the effects of F. nucleatum on cellular processes and Wnt/β-catenin signaling in relation to the progression of CRC.ConclusionThe results of this study demonstrate that F. nucleatum orchestrates a molecular network involving the direct role of Cdk5 in activating Wnt/β-catenin signaling to modulate CRC progression. Thus, in-depth investigations of F. nucleatum-associated molecular pathways may offer valuable insight into the pathogenesis of CRC, which may help further the development of treatment for this disease.

Fucoidan has many biological activities, including the inhibitory effect on the development of various cancer types. This study showed that lipopolysaccharide-induced inflammation in FHC cells (normal human colonic epithelial cells) could be reversed using fucoidan at different concentrations. The fucoidan-induced anti-inflammatory effect was also confirmed through in vivo experiments in mice. Compared to the mice of the model group, the ratio of Firmicutes/Bacteroidetes in feces increased and the diversity of gut microbial composition was restored in mice after fucoidan intervention. In colorectal cancer (CRC) cells DLD-1 and SW480, fucoidan inhibited cell proliferation and promoted cell apoptosis. It also blocked the cell cycle of DLD-1 and SW480 at the G0/G1 phase. The animal model of inflammation-related CRC showed that the incidence of tumors in mice was significantly reduced by fucoidan intervention. Furthermore, the administration of fucoidan decreased the expression levels of inflammatory factors such as TNF-α IL-6 and IL-1β in the colonic tissues. Therefore, fucoidan can effectively prevent the development of colitis-associated CRC.