唑来膦酸联合多柔比星治疗人骨肉瘤裸鼠模型的实验研究  

Combined effects of zoledronic acid with doxorubicin against human osteosarcoma xenograft model in nude mice

作　　者：刘巍峰[1] 牛晓辉[1] 张清[1] 徐海荣[1] 郝林[1] 丁易[1] 袁润英[2] 陈大福[2] 

机构地区：[1]北京积水潭医院,北京100035 [2]北京市创伤骨科研究所

出　　处：《山东医药》2011年第40期22-24,F0003,共4页Shandong Medical Journal

基　　金：首都医学发展科研基金资助项目(2005-1009)

摘　　要：目的观察唑来膦酸(ZOL)单药在体内对人骨肉瘤裸鼠移植瘤的治疗作用,明确ZOL联合DOX化疗治疗骨肉瘤的疗效。方法人骨肉瘤细胞株OS-732复苏后体外培养传代备用。48只SPF级BALB/c雌性裸鼠备用。运用组织块接种法于裸鼠右腋后皮下成瘤,实验分为6组:生理盐水对照组(NS组),DOX组,ZOL低、中、高剂量组,DOX+ZOL组。根据肿瘤倍增体积和瘤重得出抑瘤率,按照金氏公式计算Q值明确两种药物对抑制肿瘤的相互作用关系。免疫组化Ⅷ因子评价肿瘤内微血管密度(MVD)、Tunel凋亡细胞计数。结果 DOX组、ZOL低剂量组、ZOL中剂量组、ZOL高剂量组、DOX+ZOL组抑瘤率分别为43.01%、16.83%、23.88%、6.66%、49.55%,Q值为0.87,显示二者效应为单纯相加;DOX组、DOX+ZOL组凋亡指数、MVD与NS组有统计学差异,但DOX组与DOX+ZOL组间无差异。结论对于人骨肉瘤OS-732皮下移植裸鼠模型,ZOL单药干预抑瘤作用不显著;ZOL与DOX联合用药在本研究实验动物体内表现为相加作用。Objective To identify the combined effects of zoledronic acid （ZOL） with doxorubicin （DOX） against hu- man osteosarcoma xenograft model in nude mice. To evaluate the efficacy of conrbination of ZOL with DOX. Methods Es- tablishment of human osteosarcoma 0S-732 xenograft model in nude mice. 48 nude mice were divided into 6 groups： NS, DOX, ZOL （low）, ZOL （median）, ZOL （high）, DOX ＋ ZOL. To calculate the inhibition rate according to the tumor vol- ume and weight. And then to evaluate the interaction between two drugs by Q values from Jin＇ s formula. The tumors were ob- served immunohistochemical staining for VIH factor, mlcro-vessel density （MVD）, TUNEL apoptosis index （AI）. Results The inhibition rate of tumor weight of DOX, ZOL （low, median, high）, DOX ＋ ZOL groups were 43.01%, 16.83%, 23.88%, 6.66%, 49.55% respectively. The Q value was 0.87, which showed an additional effect between DOX and ZOL. There was a statistical significance between NS and DOX, DOX ＋ ZOL at MVD and AI statistical analysis, but no significance between DOX and DOX ＋ ZOL. Conclusions ZOL has no capability to inhibit proliferation of human osteosarcoma xenograft model in nude mice. DOX and ZOL play an additional effect in this experiment.

关 键 词：骨肉瘤 OS-732细胞株 唑来膦酸 多柔比星 细胞凋亡 

分 类 号：R738.1[医药卫生—肿瘤]