Abramson E C, Chang J, Mayer M, Kukla L J, Shevrin D H, Lad T E, Buschman R, Kukreja S C
University of Illinois, Chicago.
J Bone Miner Res. 1988 Oct;3(5):541-6. doi: 10.1002/jbmr.5650030510.
We have previously shown that dichlorodiamine platinum (DDP), or cisplatin, a cancer chemotherapeutic agent, is effective in the treatment of malignancy-associated hypercalcemia. In the present studies, we evaluated its effects on bovine parathyroid hormone (PTH)- or tumor-induced bone resorption in vitro in the neonatal mouse calvarial bone resorption assay. PTH alone or tumor extract (TE) of a human squamous cell lung cancer alone caused a significant increase in the bone resorption and in the number of osteoclasts in the calvaria. The addition of 3 and 10 micrograms/ml DDP inhibited the PTH- or TE-induced bone resorption. Lower doses of 1 and 2 micrograms/ml DDP, although not effective in inhibiting the PTH-induced bone resorption, were effective in lowering the TE-induced bone resorption. The number of osteoclasts was also reduced by DDP treatment. We therefore conclude that DDP is effective in the treatment of malignancy-associated hypercalcemia by virtue of its inhibitory effects on osteoclast numbers and on bone resorption.
我们之前已经表明，二氯二氨铂（DDP），即顺铂，一种癌症化疗药物，在治疗恶性肿瘤相关性高钙血症方面是有效的。在本研究中，我们在新生小鼠颅骨骨吸收试验中评估了其对牛甲状旁腺激素（PTH）或肿瘤诱导的骨吸收的体外作用。单独使用PTH或人肺鳞状细胞癌的肿瘤提取物（TE）会导致颅骨骨吸收和破骨细胞数量显著增加。添加3和10微克/毫升的DDP可抑制PTH或TE诱导的骨吸收。较低剂量的1和2微克/毫升DDP虽然对抑制PTH诱导的骨吸收无效，但对降低TE诱导的骨吸收有效。DDP治疗也减少了破骨细胞的数量。因此，我们得出结论，DDP因其对破骨细胞数量和骨吸收的抑制作用而对恶性肿瘤相关性高钙血症的治疗有效。
