Effect of parathyroid hormone(1-34) on bone metastasis of lung cancer cells in mice

Objective To investigate the effect of parathyroid hormone(1-34)(PTH) on tumor growth in a mouse model of lung cancer with bone metastasis. Methods Mouse models of proximal tibial bone metastasis of lung cancer were established in 30 female BALB/c mice. The mouse models were randomly divided into 3 groups and received injections with 40 mg/kg PTH(1-34), equal amount of solvent(blank control), or cyclophosphamide(positive control). Body weight of the mice was measured every 2 days and the right hind limb tumor growth was observed. The mice were sacrificed after 28 days for X-ray and CT examinations to observe the tumor shape, size, tibial bone density, and tumor volume. HE staining and immunohistochemistry were performed to observe the tumor morphology and pathological type, and serum concentration of serum alkaline phosphatase(ALP) was detected. Results The body weight change curves did not show significant difference between PTH(1-34) group and the blank control group(P0.05). In both PTH(1-34) group and the blank control group, X-ray and micro-CT revealed significant bone defects, and in cyclophosphamide group the bone cortex was basically intact with only mild bone destruction. The tumor volume was similar between PTH(1-34) group and the blank control group(P0.05), but significantly smaller in cyclophosphamide group(P0.05). The bone density in PTH(1-34) group was significantly greater than that in the blank control group, but lower than that in cyclophosphamide group(P0.05). Pathological examination revealed mainly osteolytic lesions mixed with bone destruction, which was severer in PTH(1-34) group and blank control group with obvious tumor cell filling of the defects; immunohistochemistry identified the tumors as adenomas. ALP activity was higher in PTH(1-34) group than in the other two group and differed significantly between the 3 groups(P0.05). Conclusion Intermittent smalldose injections of parathyroid hormone PTH(1-34) does not promote bone metastatic tumor growth in mice and increases the bone quantity around the metastatic lesions.