附子-白术药对对乳腺癌骨转移裸鼠生存时间及血清中TGF-β1、PTHrP的影响

The influence of the drug pair of Baizhu-Fuzi on the survival time of nude mice which have bone metastasis of breast cancer and the TGF-β1 and PTHrP in their serum

目的观察附子-白术药对对乳腺癌骨转移裸鼠的保护作用,并探讨其抑制骨转移的作用机制。方法采用左心室注射乳腺癌细胞MDA-MB-231BO法建立骨转移模型;裸鼠随机分为A大组和B大组;A大组分为模型组、唑来膦酸组、附子-白术药对组;B大组分为:假手术组、模型组、唑来膦酸组、附子-白术药对组;并进行相应干预。观察A大组裸鼠生存时间及体质量变化情况;观察B组裸鼠骨转移程度,抗酒石酸酸性磷酸酶染色法(tartrate resistant acid phosphatase,TRAP)观察骨转移灶中破骨细胞数量,ELISA法法检测血清中转化生长因子(TGF-β1)、甲状旁腺激素相关蛋白(PTHrP)的含有量。结果与模型组比较,药对组生存时间明显延长(P<0.05),造模后6周时体质量下降率减小(P<0.05),骨转移程度明显降低(P<0.01)、TRAP(+)细胞数量均明显减少(P<0.05),血清中TGF-β1和PHTrP的表达均显著降低(P<0.05)。结论附子-白术药对可改善乳腺癌骨转移裸鼠体质量下降,延长生存时间,减轻骨转移溶骨性损伤,其机理可能与其调控TGFβ信号通路,减少PTHrP的表达相关。

AIM To observe the drug pair Baizhu-Fuzi,s protection on the breast cancer nude mice with bony metastasis and to explore the mechanism of bone metastasis.METHODS Nude mouse models of breast cancer with bone metastasis were developed through injection of breast cancer cell MDA-MB-231BO into the left ventricle.Nude mice were randomly divided into group A and group B.Group A were subdivided into model group,zoledronic acid group and the drug pair of Baizhu-Fuzi group;and Group B were subdivided into sham-operation group,model group,zoledronic acid group and Baizhu-Fuzi group were subsequently administered with the intervention accordingly.The nude mice in group A had their surviving time and the weight changes observed;and those in group B had the degree of bone metastasis examined.Tartrate resistant acid phosphatase(TRAP)method for quantitative determination of osteoclast in bone metastasis,and ELISA method were employed to check the content of TGF-(31 and PTHrP in serum.RESULTS Compared to the model group,Baizhu-Fuzi group displayed distinctly longer survival time(P<0.05),reduced rate of weight loss 6 weeks after modeling(P<0.05),significantly declined degree of bone metastasis(P<0.01),and significantly decreased quantity of TRAP(+)cell(P<0.05)and serum TGF-pl and PTHrP(P<0.05).CONCLUSION The drug pair,Baizhu-Fuzi^s influence in TGF(3 signal path control and PTHrP expression reduction may contribute to the weight loss management,prolonged survival time,osteolytic bone defect rectification in mouse models of breast cancer with bone metastasis.