Effect of Geniposide on Malignant Progression of Osteosarcoma Cells by Regulating the JAK2/STAT3/SOCS1 Signaling Pathway
This study aims to investigate the effect of GEN(geniposide)on the malignant progression of osteo-sarcoma cells by regulating the JAK2(janus kinase 2)/STAT3(signal transducer and activator of transcription 3)/SOCS1(suppressor of cytokine signaling 1)signaling pathway.Human osteosarcoma cells(U2OS)were treated with GEN at a concentration of 2.5-40 mg/mL,and cell activity was detected using the CCK-8 method to screen for the optimal drug con-centration;U2OS cells were grouped into Control group,low,medium,and high concentration geniposide groups(GEN-L group,GEN-M group,GEN-H group),and high concentration geniposide+STAT3 activator group(GEN-H+colivelin group);cell proliferation was detected using colony formation assay;cell apoptosis was detected by flow cytometry;cell migration was detected using wound healing assay;cell invasion was detected using Transwell invasion assay;Western blot was applied to detect the expression of Cyclin D1,Ki67,Bax,Caspase-3,MMP-9,MMP-2,JAK2,STAT3,and SOCS1 proteins;nude mouse transplantation tumor experiment was applied to detect the effect of GEN on the growth of osteosar-coma transplantation tumors.5 mg/mL,10 mg/mL,and 20 mg/mL GEN were selected for the subsequent study.Compared with the Control group,the number of colony formation,scratch healing rate,number of cell invasion,and expression lev-els of Ki67,Cyclin D1,MMP-9,MMP-2,p-JAK2/JAK2,p-STAT3/STAT3 decreased in a concentration dependent manner in the GEN-L,GEN-M,and GEN-H groups,the expression of SOCS1 protein,cell apoptosis rate,and expression levels of Caspase-3 and Bax increased,in a concentration dependent manner(P＜0.05);compared with the GEN-H group,the num-ber of colony formation,scratch healing rate,number of cell invasion,and expression levels of Ki67,Cyclin Dl,MMP-9,MMP-2,p-JAK2/JAK2,p-STAT3/STAT3 obviously increased in the GEN-H+colivelin group,the expression of SOCS 1 protein,cell apoptosis rate,and expression levels of Caspase-3 and Bax obviously reduced(P＜0.05).The transplantation experiment showed that the GEN group had slower growth of transplanted tumors compared to the Control group,the volume and mass of the transplanted tumor decreased,the expression levels of p-JAK2/JAK2,p-STAT3/STAT3 reduced,SOCS1 level increased(P＜0.05).GEN can inhibit the malignant progression of osteosarcoma cells by regulating the JAK2/STAT3/SOCS1 signaling pathway.
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