Apigenin combined with cisplatin suppressed the progression of colorectal cancer by targeting the KRT23/Wnt/β-catenin signaling pathway.

Colorectal cancer (CRC) represented a pervasive manifestation of malignant neoplasia within the digestive tract. Apigenin, exhibiting a multitude of physiological attributes and pharmacological actions, has undergone extensive scrutiny for its antitumor efficacy and benign toxicity profile. Cisplatin (DDP)-centered chemotherapy constituted a pivotal aspect of multidisciplinary therapeutic strategies. Nevertheless, resistance to DDP posed a considerable impediment to the efficacy of CRC chemotherapy. The aim of this investigation was to assess the impact of combining Apigenin with DDP on the proliferation and apoptotic processes of human CRC cells, while also delving into the underlying mechanisms. HCT116 and SW480 were cultivated and subjected to treatment with Apigenin (API) either as a monotherapy or in combination with cisplatin (DDP). Cell viability, proliferation, cycle distribution, apoptosis, migration, invasion and inflammatory factors were assessed. Western blot analysis was performed to detect the protein expression levels of Glut1, HK-2, KRT23, and β-catenin. In comparison to other treatment groups, the combined API and DDP group exhibited a more potent suppressive effect on cellular proliferation, migration, invasion, and glycolysis, while also enhancing apoptotic activity. Additionally, the combined API and DDP treatment group led to a reduction in the expression levels of KRT23, β-catenin, HK-2, and Glut1. Intriguingly, this combined treatment group demonstrated significantly elevated levels of TNF-α, IL-6, and IL-8 compared to the other groups. Notably, the overexpression of KRT23 was capable of reversing the changes induced by the combined API and DDP treatment. In vivo studies further validated that the combined API and DDP treatment suppressed tumor growth by inhibiting the expression of KRT23 and β-catenin. The present findings indicated that the combination of API with DDP has the potential to enhance colorectal cancer therapy through the modulation of the KRT23/Wnt/β-catenin signaling pathway. Our research may offer fresh perspectives and novel molecular therapeutic strategies for the treatment of colorectal cancer.