Figure 5.

Efficacy evaluation of MSN-N1014 using a cancer-associated fibroblast (CAF)-educated DLD1 xenograft mouse model. (A) Tumor size over time curve. The tumor growth delay was most significant in the MSI-N1014+5-fluorouracil (5-FU) treatment group, followed by the MSI-N1014-only group, while the 5-FU-only and vehicle control groups did not show a significant difference. The insert shows representative photographs of tumor samples from each group. (B) Average body weight over time curve. No significant differences were observed among the different groups. (C) Kaplan-Meier survival curve. Mice receiving MSI-N1014 only and the combination MSI-N1014+5-FU regimen showed the highest survival ratios, while 5-FU-only and vehicle mice showed the lowest survival ratios. (D) Tumor sample Western blot analysis. Expressions of key molecules associated with oncogenic (epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (mTOR)), stemness-associated (leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) and β-catenin), drug resistance (ATP-binding cassette super-family G member 2 (ABCG2)), and inflammatory cytokines (transforming growth factor (TGF)-β1 and interleukin (IL)-6) were clearly lower in samples from MSI-N1014+5-FU and MSI-N1014-treated tumors. (E) qPCR analyses of plasma levels of miR-142-3p. Pooled blood samples from all four groups of mice were analyzed for miR-142-3p plasma levels. The combination group showed the highest level followed by NSI-N1014 alone. Numbers in red indicate the relative expression ratio. * p < 0.05; ** p < 0.01.