埃本膦酸钠对肺癌骨转移动物模型干预作用.docVIP

埃本膦酸钠对肺癌骨转移动物模型干预作用 　 作者：俞惠新，王铁生，林秀峰，齐效君，谭成，陈波，张莉，曹国宪，王博诚 【摘要】 目的 探讨埃本膦酸钠对肺癌细胞骨转移动物模型的干预作用。方法 通过贴骨接种人小细胞肺癌H446细胞制作骨转移动物模型，皮下注射埃本膦酸钠干预，利用放射学检查及病理分析等手段观察埃本膦酸钠对肺癌细胞骨转移的干预效果。结果 放射学检查显示裸鼠接种H446细胞后引起明显的肿瘤性骨损伤，骨病灶处的99TcmMDP放射性浓聚，肿瘤细胞大量侵袭至骨髓腔中。经埃本膦酸钠干预后，此骨损伤病程被明显抑制。结论 埃本膦酸钠可明显地干预肿瘤细胞对骨的侵犯，减轻肿瘤引起的骨损伤，可作为一个治疗骨转移的选择药物。 【关键词】 埃本膦酸钠; 肺癌; 骨转移; 动物模型 　　Inhibiting Effects of Ibandronate on Skektal Metastasis Model of Lung Cancer Cells 　　Abstract：Objective To investigate the inhibiting ability of Ibandronate on a skeletal metastasis model of lung caner.Methods A skeletal metastasis model of lung caner was established by injection of small cell lung carcinoma line(SCLC) H446 cells into the right leg of nude mice proximally to the tibia, and Ibandronate(5μg/animal/day) was given subcutaneously(s.c.) to the animals after radiologically small but defined osteolytic metastases were observed. Both Xray and histological assay were applied to evaluate effects of Ibandronate.Results Both Xray detection and 99TcmMDP imaging demonstrated that implant of H446 caused the development of bone lesions. Histological studies showed abnormal reacting bone formation preceded by tumor metastasizing and a number of cancer cells invading into bone marrow. But in the treated group, Ibandronate not only markedly suppressed the progression of established bone metastases lesions in nude mice, but also prevented the development of lung cancer cells in bone marrow. The reacting bone formation was limited locally.Conclusion These results suggest that Ibandronate may be a choice for the treatment of metastasis cancer in bone. 　　Key words：Ibandronate; Lung caner; Skeletal metastasis; Animal models 　　0 引言 　　双膦酸盐（Bisphosphates，BPs）对钙和骨骼矿物质具有很强的亲和性，能紧密地吸附在羟基磷灰石的表面，是一类强有力的骨吸收抑制剂[1,2]，在临床上被广泛应用于骨质疏松症的治疗[3,4]。近年来发现双膦酸盐通过抑制破骨细胞的活性阻遏肿瘤细胞在骨上的着床和发展，对肿瘤的骨转移具有抑制作用[5]。双膦酸盐用于乳腺癌及前列腺癌骨转移的治疗已有较多报道[6,7]，而对同样易于发生骨转移的肺癌研究较少[8]。我们采用一种简易方法制作了肺癌细胞H446骨转移动物模型，并评估了埃本膦酸钠对该骨转移模型的干预作用。 　　1 材料与方法 　　1.1 实验材料 　　1.1.1 主要试剂及材料 　　埃本膦酸钠（Ib