Objective To investigate the effect of CXC chemokine ligand 5 (CXCL5) on the growth of transplanted tumors of gastric cancer (GC) cells in mice via Wnt/β-catenin signaling pathway.
Methods A total of 70 GC patients (GC group) and 70 healthy individuals (healthy group) were selected as study subjects. The serum CXCL5 levels in each group were detected, and the positive rate of CXCL5 expression in GC tissues was determined using immunohistochemical staining. The relationship between CXCL5 expression and clinicopathological features was analyzed. Forty mice were divided into overexpressed CXCL5 group and control group, with 20 mice in each group. The mouse gastric cancer cell line MFC was used to establish a mouse transplanted tumor model by stable overexpression of CXCL5 and transfection with an empty vector. The growth of transplanted tumors and the survival conditions of mice in each group were recorded. The proportions of CD4+T lymphocytes, CD8+T lymphocytes, and regulatory T cells (Treg cells) in the transplanted tumor tissues of mice were detected using flow cytometry. The expressions of CXCL5 and Wnt/β-catenin signaling pathway-related proteins in the transplanted tumor tissues of mice were detected using Western blot. The mRNA expressions of cyclin D1 and proto-oncogene c-Myc (c-Myc) in the transplanted tumor tissues of mice in each group were detected using reverse transcription-quantitative real time polymerase chain reaction (RT-qPCR).
Results The serum CXCL5 level in the GC group was higher than that in the healthy group, and the difference was statistically significant (P < 0.05). The positive rate of CXCL5 expression in GC tissues was 67.14% (47/70), which was higher than 35.71% (25/70) in adjacent tissues, and the difference was statistically significant (P < 0.05). There were significant differences in tumor differentiation degree, TNM stage, and lymph node metastasis between GC patients with positive and negative CXCL5 expressions (P < 0.05). The survival rate of mice in the overexpressed CXCL5 group was lower than that in the control group, and the difference was statistically significant (P=0.048). As time elapsed, the tumor volume of mice in the overexpressed CXCL5 group was larger than that in the control group, and the difference was statistically significant (P < 0.05). The protein expressions of CXCL5, Wnt1, Wnt2, and β-catenin in the tumor tissues of mice in the overexpressed CXCL5 group were higher than those in the control group, and the differences were statistically significant (P < 0.05). The proportions of CD4+T cells and CD8+T cells in the tumor tissues of mice in the overexpressed CXCL5 group were lower than those in the control group, while the proportion of Treg cells was higher than that in the control group, and the differences were statistically significant (P < 0.05). The mRNA expressions of Cyclin D1 and c-Myc in the tumor tissues of mice in the overexpressed CXCL5 group were higher than those in the control group, and the differences were statistically significant (P < 0.05).
Conclusion The expression levels of CXCL5 in cancer tissues and serum of GC patients are upregulated. Abnormally high expression of CXCL5 may activate the Wnt/β-catenin signaling pathway, affect tumor immune activity, and promote the progression of GC.
DownLoad: