基于JAK2/STAT3信号通路探讨白藜芦醇对骨肉瘤MG-63细胞凋亡及迁移的影响

摘要 目的：研究白藜芦醇(RES)通过蛋白酪氨酸激酶2/信号转导子与激活子3（JAK2/STAT3）信号通路对人骨肉瘤体外细胞株MG-63细胞凋亡、侵袭和迁移的影响。方法：体外培养MG-63细胞，以不同浓度的RES作用于MG-63细胞。Annexin V-FITC/PI双染流式细胞术检测不同时间和不同浓度的RES对MG-63细胞凋亡的影响。划痕实验和Transwell实验检测不同时间和不同浓度的RES对MG-63细胞侵袭和迁移能力的影响。免疫印迹实验检测不同时间和不同浓度的RES对MG-63细胞磷酸化蛋白酪氨酸激酶2（p-JAK2）、磷酸化信号转导子与激活子3（p-STAT3）、凋亡相关蛋白B淋巴细胞瘤-2（Bcl-2）、Bcl-2家族促凋亡蛋白（Bax）及基质金属蛋白酶（MMP）-2、MMP-9表达的影响。结果：RES浓度越高，时间越久，MG-63细胞凋亡率越高（P<0.05）。RES浓度越高，MG-63细胞迁移和侵袭能力越弱(P<0.05)。RES处理MG-63细胞后其p-JAK2、p-STAT3、Bcl-2以及MMP-2、MMP-9的表达明显降低，而Bax蛋白表达明显升高，且p-JAK2、p-STAT3、Bax、Bcl-2以及MMP-2、MMP-9的表达水平变化具有RES浓度依赖性（P<0.05）。结论：RES可能通过调控JAK2/STAT3信号通路促使人骨肉瘤MG-63细胞凋亡，并抑制MG-63细胞侵袭和迁移。

Effects of Resveratrol on Apoptosis and Migration of Osteosarcoma MG-63 Cells Based on JAK2 / STAT3 Signaling Pathway

ABSTRACT Objective: To study the effect of resveratrol (RES) on the apoptosis, invasion and migration of human osteosarcoma cell line MG-63 through JAK2/STAT3 signaling pathway. Methods: MG-63 cells were cultured in vitro, and MG-63 cells were treated with different concentrations of RES. Annexin V-FITC/PI double staining was used to detect the effects of RES at different times and different concentrations on the apoptosis of MG-63 cells. Scratch test and Transwell invasion test were used to detect the effects of different time and different concentration of RES on the invasion and migration ability of MG-63 cells. Western blotting was used to detect the expression of phosphorylated protein tyrosine kinase 2 (p-JAK2), phosphorylated protein tyrosine kinase 3(p-STAT3), apoptosis-associated protein B lymphocytoma-2(Bcl-2), Bcl-2 family of pro-apoptotic proteins(Bax), matrix metalloproteinase(MMP)-2 and MMP-9 in MG-63 cells after treated with RES at different times points and concentrations. Results: The higher the RES concentration, and the longer the time, the higher the apoptosis rate of MG-63 cells(P<0.05). The higher the RES concentration, the weaker the migration and invasion ability of MG-63 cells(P<0.05). After RES treatment of MG-63 cells, the expression of p-JAK2, p-STAT3, Bcl-2, MMP-2 and MMP-9 were significantly decreased, while the expression of Bax was significantly increased, and the expression levels of pp-JAK2, p-STAT3, Bax, Bcl-2, MMP-2 and MMP-9 were RES concentration-dependent(P<0.05). Conclusion: RES may promote the apoptosis of human osteosarcoma MG-63 cells by regulating the JAK2/STAT3 signaling pathway, and inhibit the invasion and migration ability of osteosarcoma cells.