沙利度胺联合他莫昔芬对乳腺癌荷瘤小鼠激素水平及血管相关生长因子的影响

Effect of thalidomide combined with tamoxifen on hormone levels and vascular-related growth factors in breast cancer-bearing mice

目的探讨沙利度胺联合他莫昔芬对乳腺癌荷瘤小鼠激素水平及血管相关生长因子的影响。方法采用MCF-7细胞建立乳腺癌荷瘤小鼠模型,取建模成功48只小鼠随机分为对照组、他莫昔芬组(25 mg/kg)、沙利度胺组(50 mg/kg)、沙利度胺联合他莫昔芬组,每组各12只。连续灌胃2周,1次/d。比较各组瘤体重量、抑瘤率、激素水平、血管相关生长因子等指标。结果(1)瘤体重量与抑瘤率:模型对照组、他莫昔芬组、沙利度胺组、沙利度胺联合他莫昔芬组乳腺癌荷瘤小鼠瘤体重量分别为(2.52±0.45)、(2.07±0.40)、(2.12±0.43)、(1.15±0.35)g,他莫昔芬组、沙利度胺组、沙利度胺联合他莫昔芬组抑瘤率分别为(17.86±3.12)%、(15.87±2.54)%、(54.37±6.24)%。沙利度胺联合他莫昔芬组乳腺癌荷瘤小鼠瘤体重量明显低于他莫昔芬组、沙利度胺组,抑瘤率明显高于他莫昔芬组、沙利度胺组(t=5.996,18.129,6.061,19.796,P<0.05,P<0.01)。(2)激素水平:模型对照组、他莫昔芬组、沙利度胺组、沙利度胺联合他莫昔芬组雌激素受体-α(ER-α)平均吸光度值分别为0.712±0.015、0.421±0.010、0.385±0.012、0.212±0.007,雌激素受体-β(ER-β)平均吸光度值分别为0.105±0.005、0.192±0.007、0.178±0.006、0.245±0.008。沙利度胺联合他莫昔芬组乳腺癌荷瘤小组ER-α平均吸光度值明显低于他莫昔芬组、沙利度胺组,ER-β平均吸光度值明显高于他莫昔芬组、沙利度胺组(t=38.366、17.271、40.160、23.209,P<0.01);沙利度胺组乳腺癌荷瘤小组ER-α、ER-β平均吸光度值明显高于他莫昔芬组(t=7.897、5.260,P<0.05)。(3)血管相关生长因子:模型对照组、他莫昔芬组、沙利度胺组、沙利度胺联合他莫昔芬组乳腺癌荷瘤小鼠血清血管内皮生长因子(VEGF)含量分别为(125.12±22.34)、(96.36±13.25)、(84.42±11.35)、(72.12±9.45)ng/L,碱性成纤维细胞生长因子(bEGF)含量分别为(18.32±3.24)、(14.21±2.35)、(12.12±2.10)、(10.32±1.45)ng/L,内皮抑素(ES)含量分别为(12.32±1.45)、(14.65±1.62)、(16.12±2.02)、(18.32±2.42)μg/L。沙利度胺联合他莫昔芬组乳腺癌荷瘤小鼠血清VEGF、bEGF含量明显低于他莫昔芬组、沙利度胺组,ES含量明显高于他莫昔芬组、沙利度胺组(t=5.160、4.880、4.366、2.885、2.443、2.418,P<0.05)。结论沙利度胺联合他莫昔芬有助于抑制乳腺癌荷瘤小鼠瘤体生长。

Objective To investigate the effects of thalidomide combined with tamoxifen on hormone levels and vascular-related growth factors in breast cancer-bearing mice.Methods MCF-7 cells were used to establish a tumor-bearing mouse model of breast cancer.48 mice were randomly divided into control group,tamoxifen group(25 mg/kg),thalidomide group(50 mg/kg),thalidomide combined with tamoxifen group for 12 mice in each group.Continuous gavage for 2 weeks,once per day.The tumor weight,tumor inhibition rate,hormone level,and blood vessel-related growth factors were compared.Results(1)Tumor weight and tumor inhibition rate:The tumor weight of the model control group,tamoxifen group,thalidomide group,thalidomide combined with tamoxifen group breast cancer tumor-bearing mice were(2.52±0.45),(2.07±0.40),(2.12±0.43),(1.15±0.35)g,the tumor inhibition rates of the tamoxifen group,thalidomide group,thalidomide and tamoxifen group were(17.86±3.12)%,(15.87±2.54)%,and(54.37±6.24)%.The tumor weight of thalidomide combined with tamoxifen breast cancer-bearing mice was significantly lower than that of tamoxifen group and thalidomide group,and the tumor inhibition rate was significantly higher than that of tamoxifen group and thalidomide group(t=5.996,18.129,6.061,19.796,P<0.05,P<0.01).(2)Hormone levels:The mean luminosity values of estrogen receptor-α(ER-α)in the model control group,tamoxifen group,thalidomide group,thalidomide combined with tamoxifen group were 0.712±0.015,0.421±0.010,0.385±0.012,0.212±0.007,the mean photometric values of estrogen receptor-β(ER-β)were 0.105±0.005,0.192±0.007,0.178±0.006,and 0.245±0.008,respectively.The average luminosity value of ER-αin thalidomide combined with tamoxifen group was significantly lower than that in tamoxifen group and thalidomide group,the average luminosity value of ER-βwas significantly higher than that of tamoxifen group and thalidomide group(t=38.366,17.271,40.160,23.209,P<0.01).(3)Vascular growth-related growth factor:serum vascular endothelial growth factor(VEGF)levels in model control group,tamoxifen group,thalidomide group,thalidomide combined with tamoxifen group were(125.12±22.34),(96.36±13.25),(84.42±11.35),(72.12±9.45)ng/L,the basic fibroblast growth factor(bEGF)content was(18.32±3.24),(14.21±2.35),(12.12±2.10),(10.32±1.45)ng/L,the levels of endostatin(ES)were(12.32±1.45),(14.65±1.62),(16.12±2.02),and(18.32±2.42)μg/L.The serum levels of VEGF and bEGF in thalidomide combined with tamoxifen group were significantly lower than those in tamoxifen group and thalidomide group,the ES content was significantly higher than that of the tamoxifen group and the thalidomide group(t=5.160,4.880,4.366,2.885,2.443,2.418,P<0.05).Conclusion Thalidomide combined with tamoxifen may inhibit the growth of breast cancer in bearing mice.