[Psoralen inhibits liver metastasis of colorectal cancer by regulating Notch/Snail pathway].

This study aimed to explore the mechanism by which psoralen regulates the neurogenic gene homologous protein(Notch)/zinc-finger transcription factors(Snail) pathway to inhibit liver metastasis of colorectal cancer. SW480 cells were allocated into a blank control group, low-, medium-, and high-concentration psoralen groups, and a high-concentration psoralen + Notch activator(Jagged1) group. The cell migration, invasion, mRNA levels of matrix metalloproteinase(MMP)-2, MMP-9, epithelial cadherin(E-cadherin), neural cadherin(N-cadherin), and protein levels of Notch1 and Snail were measured. Mice were assigned into a normal group, a model group, low-, medium-, and high-dose psoralen groups, a 5-fluorouracil(5-FU) group, and a high-dose psoralen + Jagged1 group, with 12 mice in each group. Liver metastasis in mice was examined via in vivo imaging. The liver weight, number of surface nodules, liver tissue pathology, and the above mRNA and protein levels were examined. The safety of psoralen was evaluated. The results showed that compared with the blank control group, psoralen decreased the scratch healing rate, number of invasive cells, mRNA levels of MMP-2, MMP-9, and N-cadherin, and protein levels of Notch1 and Snail, while increasing the mRNA level of E-cadherin in a concentration-dependent manner. In animal experiments, compared with the model group, the low-, medium-, and high-dose psoralen groups and the 5-FU group showed alleviated pathological damage in the liver tissue, reduced region of interest(ROI) values of liver fluorescence area, liver weight, number of surface nodules, mRNA levels of MMP-2, MMP-9, and N-cadherin, and protein levels of Notch1 and Snail but increased mRNA level of E-cadherin. Moreover, psoralen functioned in a dose-dependent manner. Jagged1 reversed the inhibitory effect of high-dose psoralen on liver metastasis of colorectal cancer in mice. Psoralen did not cause significant toxicity to hematopoietic, liver, or kidney functions at the tested doses. In conclusion, psoralen may inhibit liver metastasis of colorectal cancer by suppressing the Notch/Snail pathway.