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Archive > Volume 31 Issue 6 > 2024,31(6):566-572. DOI:10.3872/j.issn.1007-385X.2024.06.004 Prev Next
Basic Research
Phillyrin inhibits the malignant biolgical behaviors of colon cancer LS180 cells through activation of the Hippo/YAP signaling pathway
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Abstract:
Objective: To investigate the effects of phillyrin (Phi) on the proliferation, migration and invasion of colorectal cancer LS180 cells by regulating the Hippo/YAP signaling pathway. Methods: Human colon cancer LS180 cells were treated with Phi at different concentrations (0, 5, 10, 20, 40, 80 μmol/L), and cell vitality at 24, 48, and 72 h was detected by MTT assay. LS180 cells were divided into the Control group, the Phi-L (5 μmol/L Phi) group, the Phi-M (10 μmol/L Phi) group, the Phi-H (20 μmol/L Phi) group, and the Phi-H+YAP inhibitor verteporfin (VP) group (20 μmol/L Phi+5 μmol/L VP). EdU was applied to detect the effects of Phi on cell proliferation in each group; scratch healing test and Transwell chamber experiments were applied to detect the effects of Phi on cell migration and invasion, respectively; the effects of Phi on Ki-67 expression rate and LATS1, YAP, p-YAP, MMP-2, MMP-9, E-cadherin and N-cadherin expressions were detected by immunofluorescence and WB. A nude mouse model of LS180 cell transplanted tumor was constructed to observe the effects of Phi on the volume and mass of transplanted tumors. Ki-67 expression rate and the expression levels of LATS1, YAP and p-YAP proteins in transplanted tumor tissues were detected by immunofluorescence and WB methods. Results: Compared with the Control group, the cell EdU positive rate, scratch healing rate, cell invasion number, Ki-67 positive rate, MMP-2, MMP-9 and N-cadherin expression levels of LS180 cells in the Phi-L, Phi-M, and Phi-H groups decreased significantly (all P<0.05), while the expression levels of E-cadherin, LATS1 and p-YAP/YAP increased significantly (all P<0.05). The inhibition of Phi on the proliferation, migration and invasion of LS180 cells was partially reversed when VP was used simultaneously. Phi significantly inhibited tumor growth in nude mice. Compared with the Control group, the tumor volume, mass and Ki-67 positive rate of nude mice in the Phi group decreased significantly (all P<0.05), while the levels of LATS1 and p-YAP/YAP increased significantly (all P<0.05). Conclusion: Phi may inhibit the malignant biological behaviors of colon cancer LS180 cells by activating the Hippo/YAP signaling pathway.
Keywords:
phillyrin (Phi) ; Hippo/YAP signaling pathway ; colorectal cancer (CRC) ; LS180 cell ; proliferation ; migration ; invasion ; mouse model
