Effects of Shikonin on the Bone Microenvironment and Heterogeneity of Spinal Tumor Cells by Regulating the High Mobility Group Protein B1-Toll Like Receptor 4-Nuclear Factor Kappa-B Signaling Pathway

Aim : The present study was conducted with an attempt to evaluate the potential therapeutic effect of shikonin on spinal tumors in vivo and its mechanism. Methods : The morphology of rat spinal tumor was observed by H&E staining, and apoptosis of rat spinal tumor was detected by transfection method and TUNEL method. In addition, the expression of cytokine mRNA and related proteins in spinal tumors of rats were detected by real-time PCR and Western blotting assays. Results : At the same period, the BBB score in the model group was significantly lower than that in the sham operation group and the shikonin group (P < 0005). Compared with the sham operation group, the BBB score in the shikonin group was significantly lower than that in the sham operation group (P < 0005), but significantly higher than that in the model group (P < 0005). Based on the RT-PCR results, the level of HMGB1 mRNA in the shikonin group was significantly lower than that of the model group (P < 0005), and the level of TLR4 mRNA in the model group was significantly lower than that in the model group (P < 0005). Moreover, the NF-kappa B mRNA level in the shikonin group was significantly lower than that in the model group (P < 0005). The expression level of HMGB1, TLR4 and NF-kappa B in the shikonin group was significantly lower than that in the model group (P < 0005). Together, the results revealed that shikonin reduced the expression of HMGB1, TLR4 and NF-kappa B mRNA and protein. The apoptosis rate of tumor cells in the shikonin group was significantly higher than that in the model group (P < 0005). The expression of caspase-3 in the shikonin group was significantly higher than that in the model group, which further indicated that shikonin could promote apoptosis of spinal tumor cells in rats. Conclusion : Shikonin has the potential to affect the heterogeneity of the bone microenvironment and spinal tumor cells by regulating the HMGB1-TLR4-NF-kappa B signaling pathway.