长春瑞滨联合依维莫司对乳腺癌细胞增殖、凋亡的影响及其机制  

Effects of combined administration of vinorelbine and everolimus on the proliferation and apoptosis of human breast cancer cells and the mechanism

作　　者：陈亮 乔红梅 杨永宏 李芳琴 CHEN Liang;QIAO Hongmei;YANG Yonghong;LI Fangqin(Department of Oncology, Baoji Affiliated Hospital of Xi＇ an Medical University, Baoji 721006, Shaanxi, China)

机构地区：[1]西安医学院附属宝鸡医院肿瘤科,陕西宝鸡7210060

出　　处：《癌症进展》2018年第3期295-298,352,共5页Oncology Progress

摘　　要：目的探讨长春瑞滨联合依维莫司对乳腺癌细胞增殖、凋亡的影响及其机制。方法以乳腺癌细胞MCF-7为研究对象,采用长春瑞滨、依维莫司干预细胞,检测长春瑞滨、依维莫司作用细胞48 h的半数抑制浓度(IC50),根据IC50设置长春瑞滨组、依维莫司组及联合组的用药浓度,以不加药物处理的细胞为对照组。MTT法检测细胞增殖活性,流式细胞术检测细胞凋亡率,Western blot检测细胞中磷脂酰肌醇-3激酶(PI3K)、磷酸化PI3K(p-PI3K)、丝氨酸/苏氨酸蛋白激酶1(AKT1)、磷酸化AKT1(p-AKT1)蛋白的表达情况。建立乳腺癌裸鼠转移瘤模型,腹腔注射长春瑞滨(2 mg/kg,qd)或依维莫司(2 mg/kg,q3d),联合组注射长春瑞滨(2 mg/kg,qd)+依维莫司(2 mg/kg,q3d),计算肿瘤体积和重量。结果随着长春瑞滨或依维莫司药物作用浓度的增加,细胞的存活率逐渐下降,且呈一定的浓度依赖性。联合组的细胞存活率低于长春瑞滨组和依维莫司组(P﹤0.05)。长春瑞滨组、依维莫司组的细胞凋亡率均高于对照组,联合组的细胞凋亡率高于长春瑞滨组和依维莫司组,差异均有统计学意义(P﹤0.05)。长春瑞滨组、依维莫司组、联合组的肿瘤体积和重量均低于对照组,联合组的肿瘤体积和重量均低于长春瑞滨组和依维莫司组,差异均有统计学意义(P﹤0.05)。长春瑞滨组和联合组细胞的p-PI3K、pAKT1蛋白表达水平均低于对照组,差异均有统计学意义(P﹤0.05);长春瑞滨组细胞的p-PI3K、p-AKT1蛋白表达水平均低于依维莫司组,高于联合组,差异均有统计学意义(P﹤0.05)。结论长春瑞滨和依维莫司在抑制细胞增殖、促进细胞凋亡、抑制肿瘤生长时具有协同作用,主要是通过抑制PI3K/AKT1信号通路的激活发挥作用。Objective To investigate the effect and mechanism of the combined therapy of vinorelbine combined with everolimus in the proliferation and apoptosis of breast cancer cells. Method MCF-7 cells were treated by vinorelbine or everolimus, and the IC50 in 48 h after treatment were detected, by which the concentration for vinorelbine group,everolimus group and combined treatment group was determined, and MCF-7 cells not containing drug was set as control. MTT assay was used to detect cell viability, flow cytometry was applied to detect the apoptosis rate in each group,and Western blot assay was utilized to detect the expression of PI3 K, p-PI3 K, AKT1 and p-AKT1. Nude mice xenograft model of human breast cancer were established, and then intraperitoneal injection of vinorelbine（2 mg/kg, qd） or everolimus（2 mg/kg, q3 d） or vinorelbine（2 mg/kg, qd） ＋ everolimus（2 mg/kg, q3 d） were administered, the tumor volume and weight were calculated. Result As the concentration of vinorelbine and everolimus increased, the cell viability decreased in a concentration dependent fashion. The cell viability in combined treatment group was lower than that in vinorelbine group and everolimus group（P〈0.05）. Compared with the control group, vinorelbine and everolimus could significantly promote apoptosis（P〈0.05）, and statistically higher apoptosis rate was observed in combined treatment group than in vinorelbine group and everolimus group, the difference was statistically significant（P〈0.05）. The volume and the weight of the tumor were significantly less and lower in vinorelbine group, everolimus group, and combined treatment group than in control group, besides, those of the combined treatment group were lower than that in vinorelbine group and everolimus group, demonstrating significant difference（P〈0.05）. The expression of p-PI3 K and AKT1 protein were lower in vinorelbine and combined treatment group than in control group, indicating statistically significant difference（P〈0.05）; the express

关 键 词：乳腺癌 长春瑞滨 依维莫司 增殖 凋亡 

分 类 号：R737.9[医药卫生—肿瘤]