人参皂苷Rh2通过调控GSK-3β/Wnt双信号通路影响骨肉瘤细胞增殖和凋亡

目的：探讨人参皂苷Rh2（Rh2）对骨肉瘤细胞增殖、凋亡、迁移和侵袭的影响，并进一步研究Rh2在骨肉瘤中抗肿瘤作用的机制。方法：分别以不同浓度的Rh2 处理骨肉瘤细胞，用MTT法检测骨肉瘤细胞活性的变化；用基质凝胶（Matrigel）侵袭和孔膜法（Transwell）迁移实验检测骨肉瘤细胞的侵袭和迁移能力的变化；用Annexin V-FITC/PI调亡检测试剂盒及流式细胞仪检测骨肉瘤细胞的调亡变化；用Western blot法检测细胞侵袭、凋亡相关蛋白的表达情况。结果：骨肉瘤细胞经过不同浓度的Rh2处理后，MTT实验结果表明Rh2在一定浓度范围内可以显著抑制骨肉瘤细胞的生长（P ＜0.05）。Matrigel侵袭和Transwell迁移实验结果表明Rh2可以有效抑制骨肉瘤细胞的侵袭与迁移（P ＜0.05）。Annexinv-FITC/PI凋亡检测试剂盒及流式细胞仪检测结果表明，Rh2可以促进骨肉瘤细胞的凋亡反应（P ＜0.05）。Western blot实验结果则显示Rh2 可以上调Bax、E-cadherin蛋白的表达，并抑制Bcl-2、PARP、MMP2、MMP9 蛋白的表达。Rh2 还可以通过激活GSK-3β并抑制β-catenin、Cyclin D1和C-myc相关蛋白来达到调控骨肉瘤细胞增殖、凋亡、迁移和侵袭反应的作用。结论：Rh2可以抑制骨肉瘤细胞的增殖并诱导其凋亡，这种作用可能是通过激活GSK-3β并抑制Wnt/β-catenin信号通路来实现的。

The effect of Ginsenoside Rh2 on proliferation and apoptosis of osteosarcoma cells through regulating GSK-3β/Wnt dual signaling pathway

Objective: To investigate the effect of Ginsenoside Rh2 (Rh2) on the proliferation, apoptosis,migration and invasion of osteosarcoma cells, and to further explore the specific antitumor mechanism of Rh2.Methods: Osteosarcoma cells were treated with different concentrations of Rh2. MTT assay was used to detect the activity of osteosarcoma cells. Matrigel invasion and Transwell migration assay were used to detect the changes in invasion and migration ability of osteosarcoma cells. Annexin V-FITC/PI apoptosis detection kit and flow cytometry were used to detect the apoptosis of osteosarcoma cells. The expression of related proteins was detected by Western blot. Results: After osteosarcoma cells were treated with different concentrations of Rh2.The results of MTT test showed that Rh2 could significantly inhibit the growth of osteosarcoma cells in a certain concentration range. Matrigel invasion and Transwell migration experiments showed that Rh2 could effectively inhibit the invasion and migration of osteosarcoma cells. In addition, annexinv FITC/PI apoptosis detection kit and flow cytometry showed that Rh2 could effectively improve the apoptosis of osteosarcoma cells. Western blot showed that Rh2 could up regulate the expression of Bax and E-cadherin, and inhibit the expression of Bcl-2, PARP, MMP-2 and MMP-9. Rh2 could also regulate the proliferation, apoptosis, migration and invasion of osteosarcoma cells via activating GSK-3β protein and inhibiting β-Catenin, Cyclin D1 and C-myc related proteins.Conclusion: Ginsenoside Rh2 can inhibit the proliferation and induce apoptosis of osteosarcoma cells, in which the activation of GSK-3β and the inhibition of Wnt/β-Catenin signal pathway may play a role.