补骨脂与蛇床子抑制乳腺癌骨转移的体内实验

Inhibition of Bone Metastasis of Breast Cancer by Fructus Psoraleae and Fructus Cnidii in vivo

目的:探讨温肾药补骨脂、蛇床子及其主要成分对乳腺癌骨转移的抑制作用。方法:将雌性BALB/c裸小鼠随机分为生理盐水组、表柔比星组、补骨脂素组、蛇床子素组和中药煎剂(蛇床子+补骨脂)组。采用人乳腺癌骨高转移细胞株MDA-MB-231BO注射裸鼠左心室制作乳腺癌骨转移动物模型,予药物干预后评价各组骨转移情况,并通过免疫组化法测定各组裸鼠骨转移灶中甲状旁腺激素相关蛋白(PTHrP)、护骨素(OPG)、核因子kB受体活化因子配基(RANKL)的蛋白表达量。结果:与生理盐水组比较,各药物组均能明显抑制裸鼠乳腺癌骨转移(P<0.05),其中补骨脂素、蛇床子素的效果优于中药煎剂,且蛇床子素的抑制作用最强;各药物组均能明显降低裸鼠骨转移灶中PTHrP和RANKL蛋白表达(P<0.05),其中补骨脂素、蛇床子素可以明显升高裸鼠乳腺癌骨转移灶中OPG蛋白表达(P<0.05)。结论:补骨脂、蛇床子及其主要成分可以在体内实验中抑制乳腺癌骨转移,其中中药单体的效果优于中药粗制剂。其作用机制可能与抑制乳腺癌细胞生长,降低乳腺癌细胞分泌促骨吸收因子PTHrP的量,从而降低成骨/基质细胞RANKL的表达,同时促进OPG的表达有关。

Objective： To study the inhibiting effect of Fructus Psoraleae and Fructus Cnidii as well as their major ingredients on the bone metastasis of breast cancer. Methods ： The female BALB/c nude mice were randomly divided into saline solution （NS） group, epirubicin group, psoralen group, ostbol group and Chinese herbal medicine Fructus Psoraleae ＋ Fructus Cnidii （FPFC） group. The animal model was established by injecting human breast cancer cells MDA-MB-231BO into the left cardiac ventricle of nude mice. The mice in different groups were administered with corresponding drugs and their bone metastases of breast cancer were evaluated. The protein expressions of parathyroid hormone-related protein （PTHrP）, osteoprotegerin （OPG）, receptor activator of nuclear factor-kB ligand （RANKL） in the bone metastasis were determined by immunohistochemistry assay. Results：Compared with the NS group, the bone metastasis was inhibited significantly in all the treatment grous （ P 〈0.05 ）. The therapeutic effects of psoralen and osthol were better than that of water decoction of herbs, with the former superior to the latter. All the drugs could significantly down-regulate the protein expression of PTHrP and RANKL （ P 〈0.05 ）, and the psoralen and osthol could upregulate the protein expression of OPG （ P 〈 0.05 ）. Conclusion ： Both Fructus Psoraleae and Fructus Cnidii can inhibit the bone metastasis of breast cancer in vivo, and the effects of monomer is better than that of water decoction. The mechanism of anti-tumor and anti-osteolysis of the drugs may involve inhibiting the growth of the breast cancer cell and reducing the protein expression of PTHrP, which may reduce the protein expression of RANKL of the osteoblasts/stromal ceils and increase the protein expression of OPG at the same time.