Mesoporous Silica-mediated Chonglou Saponin Inhibits Esophageal Cancer Cells Growth Through Regulating Fibroblast Growth Factor 19/Fibroblast Growth Factor 19 Signaling Axis

Background Chonglou saponin has been found to have certain tumor suppressor effects in a variety of cancers. However, Chonglou saponin has certain limitations and side effects in clinical application. Therefore, exploring new therapeutic strategies and mechanisms of action of Chonglou saponin is key for the treatment of esophageal cancer. Purpose This study explored the mechanism by which mesoporous silica (MSNs)-mediated saponin inhibits the growth of esophageal cancer cells through regulating the FGF19/FGFR4 signaling axis through microRNA-100 (miR-100). Materials and Methods Mesoporous silica nanoparticles-loaded polyphyllin (MSNs-PP) materials were prepared and used for Eca-109 cell culture, negative control group (NC group), MSNs-PP group (transfected with MSNs-PP), and miR-100-mimic group, miR-100-inhibitor group, BLU-554 group (transfected with FGFR4 inhibitor), FGFBP1 group (transfected with FGFR4 activator), to observe the anti-esophageal effects of MSNs-PP and the regulatory effect on miR-100, and further explore the changes in the FGF19/FGFR4 signaling axis. Results MSNs-PP were successfully prepared, and polyphyllin (PP) was found to have a positive tumor suppressor effect in esophageal cancer, with MSNs-PP being the most prominent. miR-100 has a significant effect on the activity of esophageal cancer cells. In the MSNs-PP group, miR-100-mimic was added for intervention, and the inhibitory effect on Eca-109 cell proliferation was amplified; by successfully interfering with the expression of the FGF19/FGFR4 signaling axis, FGF19 and FGFR4 expression in MSNs-PP group was low, indicating that MSNs-PP can affect the expression of FGF19/FGFR4 signaling axis to a certain extent. Through further verification, downregulating the expression of the FGF19/FGFR4 signaling axis can promote the apoptotic effect of MSNs-PP on esophageal cancer cells to a certain extent. Dual luciferase confirmed the targeting relationship between miR-100 and FGF19. MSNs-PP promotes miR-100 expression, downregulates FGF19/FGFR4, and inhibits the occurrence and development of esophageal cancer Eca-109 cells. Conclusion MSNs-PP can promote the expression of miR-100, thereby inhibiting the FGF19/FGFR4 signaling axis and inhibiting the growth of esophageal cancer cells. These findings provide a new strategy for targeted therapy of esophageal cancer based on nano-carriers and lay a theoretical foundation for the clinical application of Chonglou saponin.