目的 探究人参皂苷Rg₃通过磷脂酰肌醇3-激酶（phosphatidylinositol 3-kinase，PI3K）途径抑制胰腺癌细胞上皮间质转化及血管生成拟态的作用机制。方法 体外培养人胰腺癌SW1990细胞，使用5、10、20、40、80 μmol/L人参皂苷Rg₃处理细胞24 h。采用CCK-8法检测细胞活力并计算半数抑制浓度（half inhibitory concentration，IC₅₀），后续实验使用IC₅₀处理细胞；采用流式细胞术检测细胞凋亡；采用Transwell实验检测细胞迁移和侵袭能力；采用三维培养观察细胞血管的生成；采用qRT-PCR检测E-钙黏蛋白（E-cadherin）、N-cadherin及VE-cadherin mRNA表达；采用Western blotting检测E-cadherin、N-cadherin、VE-cadherin、PI3K及p-PI3K蛋白表达。给予PI3K激活剂740 Y-P后，考察各组细胞增殖、凋亡、迁移、侵袭、血管生成拟态及E-cadherin、N-cadherin、VE-cadherin、PI3K、p-PI3K表达情况。结果 与对照组比较，人参皂苷Rg₃组细胞增殖、迁移和侵袭能力显著降低（P＜0.001），细胞凋亡率显著升高（P＜0.001），N-cadherin、VE-cadherin及p-PI3K的表达显著下调（P＜0.01、0.001），管腔样网状结构的数目显著减少（P＜0.01），E-cadherin的表达显著上调（P＜0.01、0.001）。给予PI3K激活剂后，部分逆转了人参皂苷Rg₃对SW1990细胞增殖、迁移和侵袭、上皮间质转化和血管生成拟态的抑制作用（P＜0.05、0.01、0.001）。结论 人参皂苷Rg₃通过抑制PI3K途径的活化，进而抑制胰腺癌细胞上皮间质转化及血管生成拟态。

Objective To explore the mechanism of ginsenoside Rg₃ on inhibiting epithelial-mesenchymal transition and vasculogenic mimicry of pancreatic cancer cells through phosphatidylinositol 3-kinase (PI3K) signaling. Methods Human pancreatic cancer SW1990 cells were cultured in vitro and treated with 5, 10, 20, 40, 80 μmol/L ginsenoside Rg₃ for 24 h. CCK-8 was used to detect cell viability and half inhibitory concentration (IC₅₀) was calculated, and then the cells were treated with IC₅₀ in subsequent experiments; The apoptosis was detected by flow cytometry. Transwell experiment was used to detect migration and invasion of cells. Three-dimensional culture was used to observe the formation of cell blood vessels. The mRNA expressions of E-cadherin, N-cadherin and VE-cadherin were detected by qRT-qPCR. The protein expressions of E-cadherin, N-cadherin, VE-cadherin, PI3K and p-PI3K were detected by Western blotting. After administering PI3K activator 740 Y-P, proliferation, apoptosis, migration, invasion, vascular mimicry and expressions of E-cadherin, N-cadherin, VE cadherin, PI3K, p-PI3K of cells in each group were examined. Results Compared with control group, the proliferation, migration and invasion of SW1990 cells in ginsenoside Rg₃ group were significantly decreased (P < 0.001), apoptosis of cells was significantly increased (P < 0.001), the expressions of N-cadherin, VE-cadherin and p-PI3K were significantly down-regulated (P < 0.01, 0.001), the number of lumen-like reticular structures was significantly decreased (P < 0.01), and the expression of E-cadherin was significantly up-regulated (P < 0.01, 0.001). After administration of PI3K activator, the inhibitory effects of ginsenoside Rg₃ on proliferation, migration, invasion, epithelial-mesenchymal transition and vasculogenic mimicry of SW1990 cells were partially reversed (P < 0.05, 0.01, 0.001). Conclusion Ginsenoside Rg₃ inhibits epithelial-mesenchymal transition and vasculogenic mimicry of pancreatic cancer cells by inhibiting the activation of PI3K signaling pathway.

R285.5

浙江省自然科学基金重点项目（LZ24H280004）