Effect of Gynosaponin on the malignant biological behaviors of osteosarcoma cells by regulating the HMGB1-RAGE signaling pathway
Objective To investigate the effect of Gynosaponin(Gyp)on the malignant biological behaviors of osteosarcoma cells by regulating the high mobility group box 1-receptor for advanced glycation end products(HMGB1-RAGE)signaling pathway and its mechanism.Methods MG63 cells were treated with different concentrations of Gyp(0-400 μmol/L),and the cell viability was detected by Cell Counting Kit-8(CCK-8)assay.MG63 cells were induced with blank control,low-dose Gyp(50 μmol/L),medium-dose Gyp(100 μmol/L),high-dose Gyp(200 μmol/L),high-dose Gyp+transfection of pcDNA negative control,and high-dose Gyp+transfection of pcDNA-HMGB1.Cell proliferation,invasion,migration and apoptosis were detected by EdU assay,Transwell assay,wound healing assay and flow cytometry,respectively.Relative levels of transforming growth factor-beta(TGF-β),matrix metalloproteinase-9(MMP-9)and interleukin 6(IL-6)were measured by enzyme-linked immunosorbent assay(ELISA).Signaling pathway proteins,apoptotic proteins and epithelial mesenchymal transition(EMT)-associated proteins were examined by Western blot.An osteoporosis xenograft model in mice was created to analyze the influence of Gyp on the in vivo growth of osteoporosis.Results Treatment of Gyp at the concentration of 25-400 μmol/L significantly reduced the viability of MG63 cells.Low-dose,medium-dose and high-dose Gyp treatment significantly reduced the rate of EdU-positive cells,number of invasive cells,wound healing rate,relative levels of TGF-β,MMP-9 and IL-6,and protein levels of B-cell lymphoma-2(Bcl-2),HMGB1,RAGE,N-cadherin and vascular endothelial growth factor(VEGF);but significantly enhanced apoptotic rate and protein levels of Bax and E-cadherin in a dose-dependent manner(P＜0.05).Overexpression of HMGB1 partially reversed the inhibitory effects of Gyp on the malignant behaviors of osteoporosis cells(P＜0.05).The osteoporosis xenograft model revealed that Gyp significantly inhibited the in vivo growth of osteoporosis(P＜0.05).Conclusion The inhibitory effect of Gyp on malignant biological behaviors of osteosarcoma cells may be related to the inhibition of the HMGB1-RAGE signaling pathway.
Gynosaponinhigh mobility group box 1-receptor for advanced glycation end products(HMGB1-RAGE)signaling pathwayosteosarcomamalignant biological behavior
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