Cytotoxic effects of zoledronic acid-loaded hydroxyapatite and bone cement in malignant tumors
Cytotoxic effects of zoledronic acid-loaded hydroxyapatite and bone cement in malignant tumors
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DOI：
10.3892/ol.2017.6355
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发表时间：
2017-08-01
期刊：
影响因子：
2.9
通讯作者：
Kubo, Toshikazu
中科院分区：
文献类型：
--
作者：
Koto, Kazutaka;Murata, Hiroaki;Kubo, Toshikazu
转移性和原发性骨肿瘤是影响骨骼的恶性肿瘤。尽管随着有效化疗的发展，这些肿瘤患者的预后有所改善，但局部复发、随后的骨质溶解、骨强度退化和不可切除肿瘤的挑战仍然存在。因此，这些肿瘤的局部控制是解决这些局限性的关键策略。第三代双膦酸盐（BP），唑来膦酸（ZOL），已被证明可以减少破骨细胞，并在许多恶性肿瘤中表现出有效的抗肿瘤作用。羟基磷灰石（HA）和聚甲基丙烯酸甲酯（PMMA）骨水泥在骨科手术中用作骨移植替代品，用于植入关节成形术和骨强化，并用作抗生素等药物的缓释系统。目前，载ZOL的HA在体外或体内或载ZOL的骨水泥在体内的抗肿瘤作用尚未被描述。因此，本研究评估了负载ZOL的HA和骨水泥在恶性肿瘤细胞中的作用。这两种材料在释放ZOL后对骨肉瘤、纤维肉瘤、滑膜肉瘤、肾癌、前列腺癌和肺癌细胞具有较强的抗肿瘤作用。与ZOL负载的骨水泥相比，ZOL负载的HA的抗肿瘤作用较弱，可能是因为BP对HA表现出更高的亲和力。载ZOL骨水泥对肺转移瘤和原发性病变也有抗肿瘤作用，体内无全身毒性。这些结果表明，这些材料可能有利于治疗恶性骨肿瘤，包括转移性骨肿瘤。此外，由于这些材料已经在临床上使用，因此可以容易地实现这样的应用。
Metastatic and primary bone tumors are malignant tumors affecting the skeleton. Although the prognosis of patients with these tumors has improved with the development of effective chemotherapy, the challenges of local recurrence, subsequent osteolysis, degradation of bone strength and unresectable tumors persist. Local control of these tumors is therefore a key strategy to address these limitations. The third-generation bisphosphonate (BP), zoledronic acid (ZOL), has been demonstrated to reduce osteoclasts and exhibited potent antitumor effects in a number of malignancies. Hydroxyapatite (HA) and polymethyl methacrylate (PMMA) bone cement are used in orthopedic surgery as bone graft substitutes, for implant arthroplasty and bone strengthening, and as a sustained-release system for drugs such as antibiotics. At present, the antitumor effects of ZOL-loaded HA in vitro or in vivo or of ZOL-loaded bone cement in vivo have not been described. Therefore, the present study assessed the effects of ZOL-loaded HA and bone cement in malignant tumor cells. The two materials exerted strong antitumor effects against osteosarcoma, fibrosarcoma, synovial sarcoma, renal cancer, prostate cancer and lung cancer cells upon releasing ZOL. The antitumor effects of ZOL-loaded HA were less potent compared with those of ZOL-loaded bone cement, possibly as BPs exhibit higher affinity to HA. ZOL-loaded bone cement also exerted antitumor effects against pulmonary metastases and primary lesions, without exhibiting systemic toxicity in vivo. These results demonstrate that these materials may be beneficial for the treatment of malignant bone tumors, including metastatic bone tumors. In addition, as these materials are already in clinical use, such applications may be easily implemented.