阳和汤对裸鼠移植性乳腺癌骨转移模型作用机制的探讨

Effect mechanism of Yanghe decoction on bone metastasis of human breast cancer xenografts in nude mice

目的探讨阳和汤对裸鼠移植性人乳腺癌骨转移模型的作用及其相关调节因子的影响。方法股骨接种人乳腺癌细胞建立裸鼠乳腺癌骨转移模型。随机分为阳和汤高、低剂量组、唑来磷酸组、模型组、假手术组,动态观察各组裸鼠骨转移癌的生长情况,测量骨转移癌体积,绘制生长曲线;给药20 d后处死动物,测取瘤质量,计算抑瘤率;ELISA法检测裸鼠血清中相关调节因子PTHrP、RANKL、OPG含量的变化。结果 1.阳和汤高、低剂量组、唑来磷酸组的骨转移癌灶体积均小于模型组,差异有统计学意义(P<0.05);2.阳和汤高、低剂量组、唑来磷酸组PTHrP和RANKL含量明显低于模型组,差异有统计学意义(P<0.05),而OPG含量水平增加,RANKL/OPG的比率下降,差异有统计学意义(P<0.05)。结论 1.阳和汤有抗移植性人乳腺癌骨转移作用;2.阳和汤下调PTHrP、RANKL的含量、增加OPG的含量,抑制RANKL/OPG比率可能是其抑制乳腺癌骨转移的作用机制之一。

Objective To study the breast cancer xenografts The model of bone metas inoculating effects of Yanghe decoction on bone in nude mice and the impacts in relevant regulato metastasis ry factors. of human Methods tasis of human breast cancer xenografts in nude mice was established by breast cancer cells in femur. These mice were as follows： Yanghe decoction high -dose group and randomly divided into 5 groups low -dose group, zoledronic acid group, model group and sham-operated group. Bone metastasis tumors of different groups were observed dynamically, the volume and the growth curves of the bone metastasis tumors were measured during treatment phase. After treatment for 20 d, tumor weights were measured and the inhibition rates were calculated. The levels of associated regulatory factors of PTHrP,RAN- KL and OPG in nude mice serum were examined by ELISA enzyme-linked assay. Results The focal tumors in the Yanghe decoction high-dose group and low-dose group,zoledronic acid group were smaller than those in model group, and the differences between them were statistically signifi- cant（all P〈0.01）. Compared with model group,the content of PTHrP and RANKL were significant- ly decreased in the Yanghe decoction high-dose group and low-dose group, zoledronic acid group （all P〈0.05）, while the OPG levels were increased,and the ratios of RANKL/OPG were decreased significantly （all P 〈0.05）. Conclusion Yanghe decoction has an effects on inhibiting the bone metastasis of human breast cancer, the mechanism may be related to the down-regulation PTHrP and RANKL levels, up-regulation of OPG level and thus decreasement of RANKL/OPG ra- tio.