Effects of invigorating-spleen and anticancer prescription on extracellular signal-regulated kinase/mitogen-activated protein kinase signaling pathway in colon cancer mice model.

BACKGROUND

Colon cancer (CC) is one of the most common malignant tumors in the gastrointestinal system. Overall, CC had the third highest incidence but the second highest mortality rate globally in 2020. Nowadays, CC is mainly treated with capecitabine chemotherapy regimen, supplemented by radiotherapy, immunotherapy and targeted therapy, but there are still limitations, so Chinese medicine plays an important role.

AIM

To investigate the effects of invigorating-spleen and anticancer prescription (ISAP) on body weight, tumor inhibition rate and expression levels of proteins in extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) signaling pathway in CC mice model.

METHODS

The CC mice model were established and the mice were randomly divided into 5 groups, including the control group, capecitabine group, the low-dose, medium-dose and high-dose groups of ISAP, with 8 mice in each group, respectively. After 2 weeks of intervention, the body weight and tumor inhibition rate of mice were observed, and the expression of , , phosphorylated (), and matrix metalloproteinase 2 (MMP2) proteins in the tissues of tumors were detected.

RESULTS

Compared with the control group, the differences of body weight before and after treatment was much smaller in the groups of ISAP, with the smallest difference in the high-dose group of ISAP, while the capecitabine group had the greatest difference, indicating ISAP had a significant inhibiting effect on the growth of transplanted tumor in mice. The expression of RAS protein was decreased in the low- and medium-dose groups of ISAP, and the change of was significant in the medium- and high- dose groups of ISAP. MMP2 protein expression was significantly decreased in both the low-dose and medium-dose groups of ISAP. There were no significant changes in in the ISAP group compared to the capecitabine group, while RAS, MMP2, and C-MYC protein expression were reduced in the ISAP group. The expression level of C-MYC protein decreased after treated with ISAP, and the decrease was the most significant in the medium-dose group of ISAP.

CONCLUSION

ISAP has a potential inhibiting effect on transplanted tumor in mice, and could maintain the general conditions, physical strength and body weight of mice. The expression levels of , , and were also decreased to a certain extent. By inhibiting the expression of upstream proteins, the expression levels of downstream proteins in ERK/MAPK signaling pathway were significantly decreased. Therefore, it can be concluded that ISAP may exert an anti-tumor effect by blocking the ERK/MAPK signaling pathway and inhibiting the expression of MMP2 and c-myc proteins.