三七皂甙R1抑制PI3K/AKT通路对AML小鼠存活和Caspase-3,VEGF表达水平的影响

目的:探讨SR1对AML模型小鼠肿瘤细胞生长、侵袭、迁移及小鼠存活的影响及其作用机制。方法:采用尾静脉注射HL-60细胞的方法建立AML小鼠模型,实验组分别腹腔注射SR110、25和50 mg/kg,1次/d,连续给药1周后,检测其对各组小鼠存活率、肿瘤体积及重量的影响;免疫组织化学法检测Caspase-3和VEGF表达水平;蛋白印迹法检测PI3K/AKT信号通路磷酸化水平。结果:SR110、25和50 mg/kg可呈剂量依赖性地抑制肿瘤的生长(P<0.01,r=-0.9994、-0.9952),从而显著提高荷瘤小鼠的存活率(P<0.01);SR1能正向调节肿瘤组织中凋亡相关蛋白Caspase-3的表达(P<0.01,r=0.9855),同时负向调节肿瘤组织中迁移相关蛋白VEGF的表达(P<0.01,r=-0.9848);此外,SR1能通过显著降低肿瘤组织中p-PI3K、p-AKT的蛋白表达来剂量依赖性地减少PI3K/AKT信号通路磷酸化水平(P<0.01,r=-0.9372、-0.9953)。结论:SR1能通过抑制肿瘤细胞侵袭和迁移增加AML小鼠的存活率,其作用机制与促进Caspase-3表达、抑制VEGF表达及抑制PI3K/AKT信号通路磷酸化有关。

Effects of Sanchinoside R1 on Growth Invasion and Migration of HL-60 Cells and Survival of AML Model Mice

Objective:To investigate the effects of sanchinoside R1(SR1)on cell growth,invasion and migration of HL-60 cells,as well as survival of AML mice.Methods:AML mouse models were established by intravenous injection of HL-60 cells.The SR1 of 10,25 and 50 mg/kg was intraperitoneally injected into AML models once a day for 1 week.The survival rate of mice,tumor volume and weight were measured,and protein levels of Caspase-3 and VEGF were determined by immunohistochemistry.And protein levels of p-PI3 K,PI3 K,p-AKT and AKT were detected by Western blot.Results:SR1 significantly inhibited the growth of tumors(P<0.01,r=-0.9994,-0.9952)and increased the survival rate of mice(P<0.01).SR1 significantly increased the protein level of apoptosis-related Caspase-3(P<0.01,r=0.9855),and decreased the protein level of migration-related protein VEGF(P<0.01,r=-0.9848).The protein levels of p-PI3 K and p-AKT were down-regulated by SR1,Thus,the relative protein levels of p-PI3 K/PI3 K and p-AKT/AKT were significantly decreased(P<0.01,r=-0.9372,-0.9953).Above-mentioned effects showed a significant positive/negative correlation with the concentration of SR1.Conclusion:SR1 inhibits the growth,invasion and migration of tumor cells,and increas survival of mice through affecting expression of Caspase-3,VEGF,p-PI3 K,and p-AKT.