Yoneda T, Williams P, Rhine C, Boyce B F, Dunstan C, Mundy G R
Department of Medicine, University of Texas Health Science Center at San Antonio 78284, USA.
Cancer Res. 1995 May 1;55(9):1989-93.
Suramin is a polyanionic agent which has been found to be an effective antineoplastic agent against various human tumors including adrenal, renal and prostatic cancer, and osteosarcoma. Recently, suramin has been shown to inhibit bone resorption in organ cultures of mouse calvarial bones. In the present study, we examined the effects of suramin on increased osteoclastic bone resorption and hypercalcemia in nude mice bearing a human oral squamous carcinoma. Suramin (1 mg/mouse/injection) was administered i.p. three times a week for the first 2 weeks and then once weekly for the next 6 weeks. Blood ionized calcium levels in the suramin-treated cancer-bearing group were significantly lower than those in the untreated cancer-bearing group. Histological and histomorphometrical examination of bones of these animals showed a significant decrease in osteoclast numbers in the suramin-treated cancer-bearing animals. Suramin at a dose of 0.1 mg/mouse/injection was ineffective and 2 mg/mouse/injection was toxic, confirming its narrow effective dose. Suramin showed no effects on the growth of this squamous cancer. However, suramin markedly inhibited in vivo growth of a rat prostatic adenocarcinoma. In mouse marrow cultures, suramin decreased osteoclast-like cell formation in a dose-dependent manner. Furthermore, suramin also inhibited bone resorption in organ cultures of fetal rat long bones and resorption pit formation by isolated mature rat osteoclasts. These results show that suramin is an effective inhibitor of osteoclastic bone resorption in vitro and in vivo and suggest that suramin may be a useful agent in prevention and treatment of cancer-induced hypercalcemia. However, our results also suggest that for this indication suramin has a confined range of effective dose.
苏拉明是一种多阴离子药物，已被发现是一种有效的抗肿瘤药物，可对抗包括肾上腺癌、肾癌、前列腺癌和骨肉瘤在内的多种人类肿瘤。最近，苏拉明已被证明可抑制小鼠颅骨器官培养中的骨吸收。在本研究中，我们检测了苏拉明对荷人口腔鳞状癌裸鼠破骨细胞性骨吸收增加和高钙血症的影响。苏拉明（1毫克/小鼠/注射）腹腔注射，前2周每周3次，然后在接下来的6周每周1次。苏拉明治疗的荷癌组血离子钙水平显著低于未治疗的荷癌组。对这些动物的骨骼进行组织学和组织形态计量学检查显示，苏拉明治疗的荷癌动物破骨细胞数量显著减少。剂量为0.1毫克/小鼠/注射的苏拉明无效，而2毫克/小鼠/注射的苏拉明有毒，证实其有效剂量范围狭窄。苏拉明对这种鳞状癌的生长没有影响。然而，苏拉明显著抑制大鼠前列腺腺癌的体内生长。在小鼠骨髓培养中，苏拉明以剂量依赖性方式减少破骨样细胞的形成。此外，苏拉明还抑制胎鼠长骨器官培养中的骨吸收以及分离的成熟大鼠破骨细胞的吸收陷窝形成。这些结果表明，苏拉明在体外和体内都是破骨细胞性骨吸收的有效抑制剂，并提示苏拉明可能是预防和治疗癌症引起的高钙血症的有用药物。然而，我们的结果也表明，对于这一适应症，苏拉明的有效剂量范围有限。
