Ropivacaine inhibit the malignant biological behaviors of prostate cancer cells by inactivating the JAK2/STAT3 signaling pathway
Objective To investigate the effects of ropivacaine on the malignant biological behaviors of prostate cancer cells and its potential mechanism.Methods Human prostate cancer cells(PC-3)were treated with different doses of ropivacaine(0,1,2.5,5,10,and 15 mmol/L)to determine the optimal concentration of ropivacaine by cell survival curve analysis.PC-3 cells were cultured and randomly divided into four groups including the control group,the ropivacaine group,the colivelin group,and the combined group of ropivacaine and colivelin(JAK2/STAT3 activator)group.After treated with ropivacaine and colivelin,cell proliferation,apoptosis,migration,and invasion in each group were detected by CCK-8 assay,flow cytometry assay,cell scratch assay,and Transwell invasion assay.The expressions of apoptosis related proteins such as PARP,Bax,Bcl-2,and the expressions of EMT related proteins such as Vimentin,E-cadherin in each group were analyzed by western blot.The subcutaneous tumor nude mica models from PC-3 cells were constructed and divided into the control group,the ropivacaine group,the colivelin group,and the combined group of ropivacaine and colivelin group.After treated with ropivacaine and colivelin,the growth of subcutaneous tumors in each group was observed and their tumor cell proliferation was evaluated by Ki67 expression.The apoptosis of tumor tissues in each group was measured using TUNEL staining.The expressions of the related proteins to JAK2/STAT3 pathway in each group were examined by western blot.Results Compared with those in the control group,the apoptosis rate of cells,the protein expressions of Bax,cleaved PARP,E-cadherin,and the cell apoptosis proportion in tumor tissue in the ropivacaine group were all significantly increased(P＜0.05),but the survival rate of cells,the rate of cell migration,the number of invaded cells,the protein expressions of Bcl-2 and Vimentin,the proliferation ratio of cells in tumor tissues,the expression of p-JAK2/JAK2 and p-STAT3/STAT3 decreased(P＜0.05).On the contrary,in the colivelin group,the apoptosis rate of cells,the protein expressions of Bax,cleaved PARP,E-cadherin,and the cell apoptosis proportion in tumor tissues were all obviuosly decreased(P＜0.05),but the survival rate of cells,the rate of migration,the number of invaded cells,the protein expressions of Bcl-2 and Vimentin,the proliferation ratio of cells in tumor tissues,the expressions of p-JAK2/JAK2,p-STAT3/STAT3increased(P＜0.05).Compared with those in the ropivacaine group,the cell apoptosis rate,the protein expressions of Bax,cleaved PARP,and E-cadherin,and the cell apoptosis proportion in tumor tissues in the ropivacaine+colivelin group were all prominently reduced(P＜0.05),but the survival rate of cells,the migration rate of cells,the number of the invaded cells,the protein expressions of Bcl-2 and Vimentin,the proliferation ratio of cells in tumor tissue,the expressions of p-JAK2/JAK2,and p-STAT3/STAT3 increased(P＜0.05).Conclusion Ropivacaine obviously inhibits the activation of JAK2/STAT3 pathway to suppress the proliferation,migration,invasion activities of prostate cancer cells,promotes their apoptosis and delays their growth in nude mice,ultimately represses their malignant biological behavior.
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