人参皂苷Rg_(3)通过PI3K途径抑制胰腺癌细胞上皮间质转化及血管生成拟态  

Ginsenoside Rg_(3) inhibits epithelial-mesenchymal transition and vasculogenic mimicry of pancreatic cancer cells through PI3K signaling

作　　者：赵婷婷 王兆洪[2] 林胜璋 ZHAO Tingting;WANG Zhaohong;LIN Shengzhang(School of Medicine,Hangzhou City University,Hangzhou 310015,China;Department of General Surgery,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325027,China)

机构地区：[1]浙大城市学院医学院,浙江杭州310015 [2]温州医科大学附属第二医院普外科,浙江温州325027

出　　处：《中草药》2024年第18期6261-6268,共8页Chinese Traditional and Herbal Drugs

基　　金：浙江省自然科学基金重点项目(LZ24H280004)。

摘　　要：目的探究人参皂苷Rg_(3)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、80μmol/L人参皂苷Rg_(3)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,IC_(50)),后续实验使用IC_(50)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Rg_(3)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Rg_(3)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Rg_(3)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 Rg_(3) 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 5,10,20,40,80μmol/L ginsenoside Rg_(3) for 24 h.CCK-8 was used to detect cell viability and half inhibitory concentration(IC_(50))was calculated,and then the cells were treated with IC_(50) 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 Rg_(3) 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 Rg_(3) 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 Rg_(3) inhibits epithelial-mesenchymal transition and vasculogenic mimicry of pancreatic cancer cells by inhibiting the activation of PI3K signaling pathway.

关 键 词：人参皂苷Rg_(3) 胰腺癌 上皮间质转化 血管生成拟态 PI3K通路 

分 类 号：R285.5[医药卫生—中药学]