融合蛋白RANKL-Fc抗乳腺癌骨转移实验研究  

Study on anti-bone metastasis of breast cancer by a fusion protein of RANKL-Fc

作　　者：兰燕宇[1,2] 王静娴[1,2] 崔珺[1,2] 王爱民[1,2] 李勇军[1,2] 何彬[1,2] 刘亭[1,3] 

机构地区：[1]贵阳医学院药学院,贵阳550004 [2]贵阳医学院民族药与中药开发应用教育部工程研究中心,贵阳550004 [3]贵阳医学院贵州省药物制剂重点实验室,贵阳550004

出　　处：《中国新药杂志》2015年第2期189-194,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金(21302027);贵州省中药现代化科技产业研究开发专项项目(黔科合重G字[2013]4001);贵州省科技支撑计划社会发展攻关([2012]3079);贵州省高等学校创新能力提升计划(黔教合协同创新字[2013]04)

摘　　要：目的:探讨一种新型融合蛋白RANKL-Fc对裸鼠乳腺癌骨转移的治疗作用。方法:64只BALB-C-nu/nu雌性裸鼠随机分为假手术组、模型组及RANKL-Fc高、低剂量组。模型组及RANKL-Fc高、低剂量组左心室注射MCF-7瘤细胞悬液,假手术组左心室注射等量生理盐水,分组实验重复1次。术前2 h,RANKL-Fc高低剂量组分别肌内注射0.2,0.04 mg药物。术后35 d X线检查,取四肢骨骼行病理组织学检查,测血钙含量等。结果:病理组织学检查显示模型组骨转移发生率为44.4%。RANKL-Fc高剂量组骨转移发生率为25%,低剂量组骨转移率为32.3%。RANKL-Fc高、低剂量组与模型组血钙浓度较模型组均无显著差异。结论:由此得出,RANKL-Fc可抑制裸鼠乳腺癌骨转移,显著延长实验裸鼠存活率。该结果表明了该融合蛋白具有一定的抗乳腺癌骨转移的体内活性。Objective： To investigate the therapeutic efficacy of a novel fusion protein,RANKL-Fc,for treating bone metastasis caused by breast cancer in mice. Methods： The mice inoculated with MCF-7 by left ventricular injection were randomly divided into 3 groups,with 8 in each group： Group A was given a high dose of RANKL-Fc of 0. 2 mg,marked with “RANKL-Fc（ high） ”; group B was given a low dose of RANKL-Fc of 0. 04 mg,marked with “RANKL-Fc（ low）”; group C was given the same volume of physiological saline,marked as “vehicle”. The 8 mice in group D was given the same volume of physiological saline without the inoculation of MCF-7,marked as“control”. All experiments were in duplicate. The first administration was given two hours before the inoculation. After 35 days,X-ray examination was performed followed by pathological examination,detection for the concentration of calcium in serum and so on. Results： Histopathological examination revealed that the incidence of bone metastasis in the model group was 44. 4%,25% in the high dose group,and 32. 3% in the lower dose group. The concentration of calcium showed no significant differences among these groups. Conclusion： RANKL-Fc can inhibit bone metastasis in mice with breast cancer and prolong the survival of the mice significantly,indicating that the fusion protein has in vivo effect of anti-bone metastasis caused by breast cancer to some extend.

关 键 词：乳腺癌 骨转移 融合蛋白RANKL-Fc 

分 类 号：R914.5[医药卫生—药物化学]