血清胰岛素样生长因子-1对小鼠乳腺癌组织凋亡相关基因表达的影响

目的 在肝特异性胰岛素样生长因子1(IGF-1)基因缺失小鼠(LID小鼠)及正常小鼠体内建立原发性乳腺癌模型,比较不同血清IGF-1水平下凋亡相关基因的表达情况.方法 LID小鼠及正常小鼠各50只,用化学致癌剂7,12-二甲基苯蒽诱导原发性乳腺癌;分别随机选取25只小鼠使用人参皂甙Rg3进行干预治疗.比较各组肿瘤发生情况,应用流式细胞术及基因芯片技术分析凋亡相关基因的表达情况.结果 未管饲人参皂甙Rg3的正常小鼠乳腺癌发生率为66.7%,高于其他各组(P＜0.05);而管饲人参皂甙Rg3的LID小鼠乳腺癌发生率为12.0%,低于其他各组(P＜0.05).未管饲人参皂甙Rg3的正常小鼠肿瘤细胞凋亡比例为(2.7±0.7)%,而管饲人参皂甙Rg3的LID小鼠凋亡比例为(14.0±1.7)%.基因芯片显示正常小鼠与LID小鼠相比,LTA、LTB、TNF-α、TRAIL、TRANCE、BLK、BOK、CASP8、TRAF5、APAF1等基因表达下调,LTBR、TRAF4等基因表达上调.而应用人参皂甙Rg3治疗可改变以上基因的表达情况.结论 降低血清IGF-1水平可影响一系列凋亡相关基因的表达,从而促进细胞凋亡,对乳腺肿瘤的发生发展具有抑制作用.人参皂甙Rg3对这一效应具有协同作用.

Analysis of apoptosis-related gene expression in different serum level of insulin-like growth factor-1 in mice breast cancer tissue

Objective A stable primary breast cancer model in liver-specific insulin-like growth factor 1(IGF-1)deficient(LID)mice and control mice was established.To screen apoptosis related genes expression in different serom IGF-1 levels by gene chip and flow cytometry.Methods The LID mice and control mice were used.Induction of breast cancer was achieved by using the 7,12-dimethybenz(a)anthracene.Ginsenoside Rg3 was used to interfering therapy treatment.The incidence of breast cancer in every group was compared,and expression of apoptosis associated genes was detected by gene chip and flow cytometry.Results The incidence of tumor in none ginsenoside Rg3 injected control mice was 66.7%.The incidence of tumor in ginsenoside Rg3 injected LID mice was 12.0% which was significantly lower than any other group(P<0.05).The apoptosis percentage in none ginsenoside Rg3 injected control mice was(2.7±0.7)%.The apoptosis percentage in ginsenoside Rg3 injected LID mice was(14.0±1.7)%.The results of gene chip indicated that in contrast to LID mice,LTA,LTB,TNF-α,TRAIL,TRANCE,BLK,BOK,CASP8,TRAF5,and APAF1 genes were down-regulated,and LTBR,TRAF4 genes were up-regulated in the breast cancer tissues of control mice.Application of ginsenoside Rg3 therapy could change the expression of these genes.Conclusions Circulating IGF-1 levels play a role in the onset and development of breast cancer.Degrade serum IGF-1 level is able to promote apoptosis by affecting the expression of a series of apoptosis related genes consequently inhibit the growth of breast cancer.There was a synergistic effect with the application of ginsenoside Rg3.