槲皮素对内分泌耐药乳腺癌三苯氧胺治疗增敏作用的体内研究

发布时间：2018-12-18 07:03

【摘要】：目的:探讨槲皮素(QUE)对内分泌耐药乳腺癌三苯氧胺(TAM)治疗的增敏作用。方法:用大剂量TAM冲击法构建TAM耐药乳腺癌细胞株MCF-7/TAM-R并移植裸鼠后,将荷瘤鼠随机分为4组,分别给予溶媒(对照组)、QUE 50 mg/kg 1次/2 d(QUE组)、TAM 5 mg/kg 1次/d(TAM组)、QUE 50 mg/kg 1次/2 d+TAM 5 mg/kg 1次/d(QUE+TAM组)处理,动态观测各组荷瘤鼠的一般情况与瘤体体积的变化,于给药21 d后,处死各组荷瘤鼠,检测瘤体质量及瘤组织ERα、HER-2、pMAPK、MAPK、pAkt、Akt蛋白的表达。结果:给药过程中,QUE+TAM组和QUE组裸鼠摄食减少、体质量减轻,对照组与TAM组裸鼠无明显异常;至第12天开始,QUE+TAM组瘤体生长呈下降趋势,且第21天明显下降(P0.05),其余各组瘤体均呈持续增长。与对照组比较,QUE+TAM组瘤体质量明显减轻(P0.05),而其余两组均无统计学差异(均P0.05);QUE+TAM组和QUE组瘤组织中ERα蛋白高表达,HER-2、pMAPK、pAkt蛋白低表达,而TAM组上述蛋白表达均无明显差异,各组非磷酸化的MAPK、Akt蛋白表达均无明显差异。结论:QUE能恢复内分泌耐药乳腺癌对TAM的敏感性,可能与其下调HER-2及其下游信号pMAPK、pAkt的表达,并上调ERα的表达有关;QUE有潜在的毒副作用,其安全范围及有效剂量有待进一步探讨。
[Abstract]:Objective: to investigate the sensitizing effect of quercetin (QUE) on tamoxifen (TAM) in endocrine-resistant breast cancer. Methods: the TAM resistant breast cancer cell line MCF-7/TAM-R was constructed by high dose TAM shock method and transplanted into nude mice. The mice were randomly divided into 4 groups: control group (), QUE 50 mg/kg once / 2 d (QUE group). TAM 5 mg/kg / d (TAM group), QUE 50 mg/kg 1 / 2 d TAM 5 mg/kg 1 / d (QUE TAM group were treated. The general situation and tumor volume of each group were observed dynamically. After 21 days of administration, the changes of tumor volume in each group were observed. The tumor mass and the expression of ER 伪 and HER-2,pMAPK,MAPK,pAkt,Akt protein were detected. Results: during the course of administration, the intake and body weight of nude mice in, QUE TAM group and QUE group were decreased, but there was no obvious abnormality in control group and TAM group. From the 12th day, the tumor growth in, QUE TAM group showed a downward trend, and decreased significantly on the 21st day (P0.05), and the other groups showed a sustained increase in tumor growth. Compared with the control group, the tumor mass of, QUE TAM group was significantly reduced (P0.05), while the other two groups had no statistical difference (P0.05). The expression of ER 伪 protein was high and HER-2,pMAPK,pAkt protein was low in QUE TAM group and QUE group, but there was no significant difference between TAM group and TAM group. There was no significant difference in the expression of non-phosphorylated MAPK,Akt protein in all groups. Conclusion: QUE can restore the sensitivity of endocrine resistant breast cancer to TAM, which may be related to the down-regulation of pMAPK,pAkt expression of HER-2 and its downstream signal, and the up-regulation of ER 伪 expression. QUE has potential side effects, and its safe range and effective dose need to be further explored.
【作者单位】：广东医科大学附属深圳南山医院甲乳外科;深圳大学医学部;中山大学实验动物中心;
【基金】：广东省医学科研基金资助项目(A2014664)
【分类号】：R737.9

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