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Aim: High mobility group protein box1 (HMGB1) and its receptor-receptor for advanced glycation end products (RAGE) are pivotal factors in the development and progression of many types of tumor,but the role of HMGB1-RAGE axis in prostate cancer (PCa) remains unclear.Here, we report the role of HMGB1-RAGE axis in the biological behaviors of PC-3 cell lines.Methods: We firstly purified rHMGB1 through 6xHis-Ni-NTA chromatography.Using the technique of RNA interference, the expression of RAGE was downregulated in the PC-3 cell lines.The biological effect of HMGB1 and RAGE on PC-3 cells proliferation,migration, and apoptosis was measured by CCK-8, migration assays, and flow cytometry.Results: We show that intracellular overexpression HMGB1 and extracellular rHMGB1 promotes cellular proliferation, migration,and anti-apoptosis.However, once knocking down RAGE, rHMGB1 cannot promote cellular proliferation,migration, and anti-apoptosis.Conclusion: The results demonstrate that HMGB1 activates RAGE signaling pathways to promote cellular proliferation, migration, and anti-apoptosis, in PC-3 cell lines.HMGB1-RAGE axis may become a potential target in Pca therapy.