Effects of ulinastatin on the malignant progression of ovarian cancer cells by regulating the RhoA/ROCK signaling pathway
GAO Wenjun
WANG Haina
XU Xiaoyu
Abstract：Objective To explore the effects of ulinastatin(UTI)on the malignant progression of ovarian cancer cells and the involvement of the Ras homolog gene family member A-Rho associated coiled coil containing protein kinase(RhoA-ROCK)signaling pathway.Methods Human ovarian cancer SKOV3 cells were cultured and treated with blank control,low-dose,medium-dose and high-dose UTI,or high-dose UTI+RhoA activator LPA.Cell proliferation,apoptosis,migration and invasion were detected by EdU assay,Annexin V-FITC/PI staining,wound healing assay and Transwell assay,respectively.Western blot was applied to detect protein levels of cyclin D1,p21(negative regulator of cell cycle),cleaved caspase-3,B-lymphoblastoma-2(Bcl-2),matrix metalloproteinase-2(MMP-2),MMP-9,E-cadherin,N-cadherin,vimentin,RhoA,ROCK1 and ROCK2.Results Compared with those of blank control,SKOV3 cells treated with low-dose,medium-dose and high-dose UTI had significantly lower EdU-positive rate,wound healing rate,invasive cell number,protein levels of Cyclin D1,Bcl-2,MMP-2,MMP-9,N-cadherin,Vimentin,RhoA,ROCK1 and ROCK2,but significantly higher apoptotic rate and protein levels of p21,cleaved caspase-3 and E-cadherin in a dose-dependent manner(P＜0.05).Compared with those treated with high-dose UTI,SKOV3 cells treated with high-dose UTI+LPA had significantly higher EdU-positive rate,wound healing rate,invasive cell number,protein levels of Cyclin D1,Bcl-2,MMP-2,MMP-9,N-cadherin,Vimentin,RhoA,ROCK1 and ROCK2,but significantly lower apoptotic rate and protein levels of p21,cleaved caspase-3 and E-cadherin(P＜0.05).A xenograft model in nude mice showed that UTI-induced nude mice had significantly slower growth of ovarian cancer,lower tumor weight and lower expression levels of RhoA,ROCK1 and ROCK2 than those of controls(P＜0.05).Conclusion UTI inhibits the malignant progression of ovarian cancer cells by inhibiting the RhoA/ROCK signaling pathway.
Keywords：Ras homolog gene family member A-Rho associated coiled coil containing protein kinase signaling pathwayovarian cancerproliferationapoptosismigrationinvasionepithelial mesenchymal transition
Publication Date：2025-05-26
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 709-714 )