目的 建立骨肉瘤MNNG/HOS裸小鼠模型,并研究曲古抑菌素A(TSA)体内抗肿瘤作用.方法 采取皮下悬液注射法,建立人骨肉瘤裸小鼠模型.人骨肉瘤MNNG/HOS细胞株体外传代培养后,将2×106细胞悬液注入裸小鼠股外侧皮下,观察肿瘤生长情况.荷瘤小鼠行小动物Micro-CT成像系统检查,肿瘤组织常规HE染色并镜检.相同方法建立此种骨肉瘤裸小鼠模型,待肿瘤直径达10～20 mm时,随机分为对照组(注射含体积分数5％DMSO的生理盐水),TSA组(注射TSA,1 mg/kg)和环磷酰胺(CTX)组(注射CTX,20 mg/kg),每隔3d注射1次,同时测量肿瘤直径及荷瘤鼠体质量,绘制肿瘤生长曲线及裸小鼠体质量变化曲线.结果 裸小鼠接种细胞株2周后,均有局部肿瘤形成.4周后,小动物Micro-CT成像系统可见骨质破坏,光镜下可见骨肉瘤细胞及其直接形成的肿瘤性骨样组织,骨肉瘤细胞在横纹肌间浸润性生长,成骨作用明显.在本实验建立的动物模型体内,TSA可明显抑制肿瘤的生长(P＜0.05),对照组与实验组无明显的体质量差异.结论 成功建立了骨肉瘤MNNG/HOS裸小鼠模型；TSA在骨肉瘤裸小鼠模型体内,可明显抑制肿瘤的生长.%Objective To establish an animal model of human osteosarcoma in nude mice, and use the model to investigate the antitumor activity of Trichostatin A with this animal model. Methods Nude mice received MNNG/HOS cell suspensions was subcutaneously injected into nude mice with the concentration of 2×106 to develop growing tumor. Tumor-bearing mice were examined by Micro-CT imaging system; the tumor tissue was observed by microscopic examination after HE staining. The animal model of human osteosarcoma was established. When subcutaneous tumors were 10-20 mm, mice were randomly divided into the control group (n=6), TSA group (n=6) and CTX group (n=6), the TSA group was treated with TSA (1 mg/kg); CTX group was treated with CTX (20 mg/kg); and control animals were treated with vehicle containing saline with 5% DMSO. Mice were injected every three days. Measure the size of tumor and the weight of tumor-bearing mice was recorded. The tumor growth curve and nude mice weight change curve were drawn. Results Two weeks after the inoculation, local tumor was formed. Four weeks later, bone destruction was visible in Micro-CT imaging system; osteoid tissue formed by osteosarcoma cells could be seen under light microscope and osteoplastic process was ubiquitous. TSA significantly inhibited tumor growth (P<0.05). No significant body weight difference or signs of overt toxicity was noticed between TSA and control group. Conclusion The animal model of osteosarcoma was successfully established, which will provided the basis of animal experiments for clinical studies of osteosarcoma. TSA significantly inhibited tumor growth of osteosarcoma in vivo.
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