notoginsenoside-r1 and Leukemia--Myeloid--Acute

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.. 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-PI3K, PI3K, p-AKT and AKT were detected by Western blot.. 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-PI3K and p-AKT were down-regulated by SR1, Thus, the relative protein levels of p-PI3K/PI3K 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.. SR1 inhibits the growth, invasion and migration of tumor cells, and increas survival of mice through affecting expression of Caspase-3, VEGF, p-PI3K, and p-AKT.. 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.. 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.. 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SR1 10、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.. SR1 10、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).. 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.

Topics: Animals; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Ginsenosides; HL-60 Cells; Humans; Leukemia, Myeloid, Acute; Mice; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Signal Transduction