他莫昔芬对Luminal A型乳腺癌大鼠的影响研究

Effect of tamoxifen on Luminal A breast cancer

目的研究他莫昔芬对Luminal A型乳腺癌大鼠Src同源区2蛋白酪氨酸磷酸酶1(SHP-1)表达水平的影响。方法选取健康雌性未孕SD大鼠80只,其中62只用7,12-二甲基苯并蒽(DMBA)灌胃建立Luminal A型乳腺癌模型,空白组18只用等量食用花生油灌胃。将造模成功的54只大鼠随机分为模型组、对照组和实验组,各18只。实验组给予0. 6 mg·m L^(-1)枸橼酸他莫昔芬溶液1 m L,灌胃,每天1次;对照组给予0. 15 mg·m L^(-1)来曲唑溶液1 m L,灌胃,每天1次;模型组及空白组分别给予蒸馏水1 m L,灌胃,每天1次;各组均连续给药3周。观察各组大鼠的肿瘤体积、瘤重及抑瘤率、血清性激素水平、肿瘤组织SHP-1 mRNA及SHP-1蛋白、细胞外调节蛋白激酶1/2(p-Erk1/2)、β-连环蛋白(β-catenin)、细胞周期蛋白(Cyclin D1)蛋白表达水平进行检测。结果治疗后,模型组、实验组和对照组肿瘤体积分别为(5. 01±0. 58),(1. 15±0. 09)和(1. 53±0. 18) cm^3,瘤重分别为(5. 83±0. 67),(1. 84±0. 25)和(2. 49±0. 31) g,实验组和对照组抑瘤率分别为68. 44%和57. 29%,差异均有统计学意义(均P <0. 05)。空白组、模型组、实验组和对照组肿瘤组织SHP-1 mRNA分别为2. 58±0. 36,0. 72±0. 09,1. 91±0. 27和1. 42±0. 18,SHP-1蛋白分别为2. 16±0. 27,0. 62±0. 08,1. 73±0. 24和1. 35±0. 15,差异均有统计学意义(均P <0. 05)。结论他莫昔芬能有效抑制Luminal A型乳腺癌大鼠肿瘤生长,其作用可能与上调SHP-1基因及其相关蛋白表达有关。

Objective To analyze the effect of tamoxifen on the expression of Src homology 2 protein tyrosine phosphatase 1(SHP-1)in Luminal A breast cancer.Methods Eighty healthy female nonpregnant SD rats were selected,62 of them were established Luminal A breast cancer models by intragastric administration of 7,12-dimethylbena anthracene(DMBA),18 rats in blank group received intragastric administration of peanut oil of equal amount.Fifty-four model rats were randomly divided into model group,experimental group and control group,each group 18 rats.Experimental group was given 0.6 mg·mL-1 tamoxifen citrate solution 1 mL for gastric perfusion,qd;control group was given 0.15 mg·mL-1 letrozole solution 1 m L for gastric perfusion,qd;model group and blank group were given distilled water 1 mL for gastric perfusion,qd.Each group was given continuous administration for 3 weeks.The tumor volume,tumor weight and tumor inhibitory rate in rats,serum sex hormone levels,the expression levels of SHP-1 mRNA and SHP-1 protein,extracellular regulated protein kinase 1/2(p-Erk1/2),β-catenin(β-catenin)and CyclinD1 protein in tumor tissues of four groups were detected.Results After treatment,the tumor volume in model group,experimental group and control group were(5.01±0.58),(1.15±0.09)and(1.53±0.18)cm3,tumor weight were(5.83±0.67),(1.84±0.25)and(2.49±0.31)g,the tumor inhibition rates in experimental group and control group were 68.44%and 57.29%,all with significant difference(all P<0.05).The levels of SHP-1 mRNA in tumor tissues in blank group,model group,experimental group and control group were 2.58±0.36,0.72±0.09,1.91±0.27 and 1.42±0.18,SHP-1 protein were 2.16±0.27,0.62±0.08,1.73±0.24 and 1.35±0.15,all with significant difference(all P<0.05).Conclusion Tamoxifen can effectively inhibit tumor growth in Luminal A breast cancer rats,the mechanism may be related to regulate serum sex hormone levels,and up regulation of SHP-1 gene and its related protein expression.