比卡鲁胺联合紫杉醇对雄激素受体阳性三阴性乳腺癌MDA-MB-231细胞的增殖抑制作用  

Inhibitory effect of bicalutamide and paclitaxel on proliferation of androgen receptor-positive triple negative breast cancer MDA-MB-231 cells

作　　者：丁钥 许焱[1] 丁丽[1] 朱小泉[1] 张永强[1] Ding Yue, Xu Yan, Ding Li, Zhu Xiaoquan, Zhang Yongqiang.(Department of Medical Oncology, Beijing Hospital/ National Center of Gerontology, Beijing 100730, China)

机构地区：[1]北京医院国家老年医学中心肿瘤内科,100730

出　　处：《中华乳腺病杂志（电子版）》2018年第3期135-140,共6页Chinese Journal of Breast Disease(Electronic Edition)

摘　　要：目的探讨比卡鲁胺(BIC)联合化疗药物紫杉醇(PTX)对雄激素受体(AR)阳性的三阴性乳腺癌MDA-MB-231细胞的增殖抑制作用及可能的作用机制。方法采用CCK-8试剂盒观察不同浓度的BIC(0.1、1.0、10.0μmol/L)和PTX(0.1、1.0、10.0、100.0、1 000.0、10 000.0 nmol/L)以单药及不同联合给药方式处理后,对MDA-MB-231细胞增殖的抑制作用。细胞增殖抑制率比较采用单因素方差分析。组间两两比较采用LSD法。选取10 nmol/L PTX及10 nmol/L DMSO分别处理MDA-MB-231细胞样品(各3个)72 h,采用生物信息学方法分析样品的相关基因表达芯片数据,采用校正t检验筛选出差异基因。结果使用不同浓度的BIC分别处理MDA-MB-231细胞24、48、72 h后,各组MDA-MB-231细胞增殖抑制率在不同时间点差异均有统计学意义(F=4.124、8.189、4.139,P=0.037、0.004、0.032)。BIC 10.0μmol/L组MDA-MB-231细胞增殖抑制率在48 h最高,为(12.9±5.5)%。不同浓度的PTX分别处理MDA-MB-231细胞24、48、72 h后,不同浓度组MDA-MB-231细胞增殖抑制率在不同时间点差异均有统计学意义(F=8.407、47.432、14.907,P均<0.001)。PTX在48 h时对MDA-MB-231细胞的半数抑制浓度(IC50)为5 380.0 nmol/L。5 000.0 nmol/L PTX单药或联合不同浓度(0.1、1.0、10.0μmol/L)的BIC同时处理MDA-MB-231细胞48 h后,5 000.0 nmol/L PTX单药处理组与3个实验组中细胞增殖抑制率分别为(53.2±2.7)%、(53.2±3.1)%、(51.7±3.4)%、(51.0±2.3)%,组间差异无统计学意义(F=0.831,P=0.492)。采用5 000.0 nmol/L PTX和10.0μmol/L BIC以不同的序贯方式联合给药处理MDA-MB-231细胞(PTX 24 h+BIC 24 h组、BIC 24 h+PTX 24 h组、PTX 48 h+BIC 24 h组、BIC 48 h+PTX 24 h组),并用5 000.0 nmol/L PTX(PTX 48 h组)和10.0μmol/L BIC(BIC 48 h组)单药处理及同时联合给药(PTX 48 h+BIC 48 h组)分别处理MDA-MB-231细胞后,各组间细胞增殖抑制率差异有统计学意义(F=241.466,P<0.001)。其中,两两比较结果显示,PTX 24 h+BIC 24 h组细胞增殖抑�Objective To investigate the inhibitory effect of bicalutamide（ BIC） combined with paclitaxel（ PTX） on the proliferation of androgen receptor（ AR）-positive triple negative breast cancer MDAMB-231 cells and its possible mechanism. Methods The CCK-8 kit was used to determine the effect of BIC（ 0. 1,1. 0,10. 0 μmol/L） and PTX at different concentrations（ 0. 1,1. 0,10. 0,100. 0,1000. 0,10 000. 0 nmol/L） in monotherapy or in sequential combination of both on the proliferation of MDA-MB-231 cells. Inhibition rate was compared using one-way analysis of variance. The pairwise comparison was performed using the LSD method. MDA-MB-231 cells were treated with 10 nmol/L PTX and 10 nmol/L DMSO respectively for 72 h. Three cell samples were taken in each group to analyze the relevant gene expression profiling in array using a bioinformatic method. The adjusted t test was used to screen out differential genes.Results After MDA-MB-231 cells were treated with different concentrations of BIC for 24,48 and 72 h,respectively,the inhibition rates of MDA-MB-231 cells were statistically different at different time points（ F =4. 124,8. 189,4. 139,P = 0. 037,0. 004,0. 032）. The inhibition rate of MDA-MB-231 cells reached the highest [（ 12. 9 ± 5. 5） %] at 48 h after the treatment of 10. 0 μmol/L BIC. The inhibition rates of MDA-MB-231 cells were significantly different at different time points（ F = 8. 407,47. 432,14. 907,P0. 001） after the treatment of PTX at different concentrations. The half inhibitory concentration（ IC50） of PTX in MDA-MB-231 cells at 48 h was 5 380. 0 nmol/L. After 48 h treatment of 5 000. 0 nmol/L PTX alone or combined with 0. 1,1. 0,10. 0 μmol/L BIC,the inhibition rate of MDA-MB-231 cells was（ 53. 2 ± 2. 7） %,（ 53. 2 ± 3. 1） %,（ 51. 7 ± 3. 4） %,（ 51. 0 ± 2. 3） % in PTX monotherapy group and three experimental groups,respectively,indicating no significant difference（ F = 0. 831,P = 0. 492）. MDA-MB-231 cells were treated with sequential combination of 5

关 键 词：乳腺肿瘤 雄激素受体拮抗剂 化学疗法 联合药物疗法 早期生长反应蛋白质1 

分 类 号：R737.9[医药卫生—肿瘤]