Based On The IL6R/JAK-STAT Signaling Pathway To Regulate The Malignant Proliferation Of Osteosarcoma To Explore The Mechanism Of Yiliu Decoction Against Osteosarcoma Pathway

Objective: The purpose of this study was to explore the mechanism of Yiliu Decoction in anti-osteosarcoma.The relationship between Yiliu Decoction,IL6 R / JAK-STAT signaling pathway and invasion,proliferation and apoptosis of osteosarcoma cells was verified by cell and animal experiments.It is clarified that Yiliu Decoction has the effect of anti-osteosarcoma development.Methods: Three osteosarcoma-related datasets(GSE14359,GSE12865,GSE19276)were downloaded from the GEO database,including 9 normal tissue samples and 74 osteosarcoma tissue samples.DEGs and WGCNA were performed on the merged and corrected datasets by R language,and the results were intersected.Then,functional enrichment analysis and PPI were performed on the intersected genes,and cytoscape was used for network visualization.The top 10 genes in degree were calculated as core genes by Cytohubba package.In addition,GEO datasets GSE16088 and GSE39262 were used to test the top ten genes of degree.Transwell invasion chamber assay,MTT colorimetric assay and tunel cell experiments were used to verify whether Yiliu Decoction could inhibit OS cell invasion and proliferation and promote OS cell apoptosis.The effect of Yiliu Decoction on the expression of IL6 R was observed by q RT-PCR and Western Blot in animal experiments,and whether it could down-regulate the expression of IL6 R and lead to the down-regulation of JAK-STAT signaling pathway and inhibit the growth of osteosarcoma.Results: The results of bioinformatics analysis showed that IL6 R was highly expressed in OS tissues,and the intersection genes were mainly enriched in cytokine-cytokine receptor interaction,neuroactive ligand-receptor interaction and Jak-STAT signaling pathways.The top 10 genes of degree in PPI network were IL6 R,MPO,HP,DEFA4,CAMP,LTF,ARG1,AZU1,CTSG and PGLYRP1.T test results showed that the expression of key gene IL6 R in osteosarcoma group was higher than that in normal group,p<0.05.But,MPO,HP,DEFA4,CAMP,LTF,ARG1,AZU1,CTSG and PGLYRP1 were not statistically significant(p > 0.05).Transwell invasion chamber assay and MTT colorimetric assay showed that Yiliu Decoction could inhibit the proliferation and invasion of osteosarcoma cells,and Tunel assay showed that Yiliu Decoction could promote the apoptosis of OS cells.Animal experiments qrt-PCR confirmed that Yiliu Decoction can down-regulate the expression of IL6 R.Western Blot experiments verified that IL6 R inhibitors can inhibit the expression of JAK-STAT signaling pathway by inhibiting the expression of IL6 R.Yiliu decoction can down-regulate the expression of IL6 R,which leads to the down-regulation of JAK-STAT signaling pathway and inhibits the growth of osteosarcoma.Conclusion(s): IL6 R is highly expressed in osteosarcoma tissues,and JAK-STAT signaling pathway is mainly involved in many important biological processes such as cell proliferation,differentiation,apoptosis and immune regulation.The expression of JAK-STAT signaling pathway can be down-regulated by inhibiting the expression of IL6 R.By inhibiting the expression of IL6 R,the JAK-STAT signaling pathway was down-regulated,which inhibited the proliferation of osteosarcoma cells and promoted their apoptosis.