Vitamin P Significantly Inhibits the Expression of Ki67 and VEGF and Promotes the Apoptosis of Colorectal Cancer Cells.

BACKGROUND

Colorectal cancer is a common malignant tumor of the digestive tract, with a high incidence and mortality rate. Ki67 and vascular endothelial growth factor (VEGF) play important roles in tumor cell proliferation and angiogenesis. Vitamin P is a natural flavonoid compound with various biological activities.

OBJECTIVES

To explore the effects of vitamin P on the proliferation, angiogenesis, and apoptosis of colorectal cancer cells and its underlying molecular mechanisms.

METHODS

In vitro cultivation of human colorectal cancer cell lines (HCT116 and SW480) was performed. Vitamin P was added to the cells in varying quantities. Cell proliferation was identified using the CCK-8 technique. The flow cytometry method was used to determine the proportion of apoptotic cells. Real-time fluorescence quantitative PCR and Western blot methods were used to measure the expression levels of the VEGF and Ki67 genes and proteins. Secretion of VEGF was observed via immunofluorescence staining.

RESULTS

Vitamin P treatment significantly inhibited the proliferation of colorectal cancer cells in a dose-dependent manner. The half-maximal inhibitory concentrations (ICs50) at 48 hours were 72.3 μM (HCT116) and 85.6 μM (SW480). Moreover, in the vitamin P treatment group (42.7 - 68.9% and 35.4 - 61.2%), the secretion of VEGF decreased by 52.3 - 79.8%. The percentage of apoptotic cells induced by 20 - 80 μM vitamin P increased from 5.3% in the control group to 18.6 - 37.9%, with increased caspase-3 activity. In vivo experiments showed that vitamin P significantly inhibited the growth of colorectal cancer transplanted tumors and reduced the expression of Ki67 and VEGF in the tumors. Meanwhile, vitamin P treatment induced apoptosis of tumor cells, and this effect was closely related to the regulation of the Bax/Bcl-2 ratio and the promotion of caspase-3 activation. Vitamin P may play a regulatory role by inhibiting the phosphorylation of the STAT3 signaling pathway and downregulating the expression of proteins related to the PI3K/AKT pathway.

CONCLUSIONS

Vitamin P can inhibit the malignant biological behavior of colorectal cancer cells by suppressing Ki67-mediated cell proliferation, blocking VEGF-related angiogenesis pathways, and activating mitochondrial apoptotic pathways.