靶向短肽介导的肿瘤抑素活性T3片段对骨肉瘤的疗效

摘要

目的 探讨靶向短肽介导的肿瘤抑素(tumstatin)活性T3片段对骨肉瘤裸鼠皮下移植瘤的抑瘤效果.方法 人工合成肿瘤抑素活性T3片段并加载对骨肉瘤血管有靶向结合能力的7肽.在体外,通过细胞凋亡抑制(MTS)法、细胞迁移抑制实验检测该活性肽对人脐静脉血管内皮细胞的抑制作用.体内实验,选取裸鼠50只,制备荷骨肉瘤裸鼠模型,剔除瘤体较大或较小的裸鼠,将剩余荷瘤裸鼠分为4组,每组6只,分别给予T3肽、靶向-T3肽、化疗药物(CTX)及磷酸盐缓冲液(PBS)干预治疗.治疗完成后完全剥离肿瘤称重,并进行肿瘤组织免疫组化染色、裸鼠肺组织HE染色,以分析靶向-T3肽对骨肉瘤血管生成及侵袭力的抑制效果.结果 体外环境下,T3肽及靶向-T3肽均有效抑制人脐静脉血管内皮细胞的增殖.体内实验,靶向-T3肽组平均瘤重(1.104±0.247)g,其肿瘤抑制率为46.9%;T3肽组平均瘤重(1.484±0.369)g,其肿瘤抑制率为28.6%;各治疗组间肿瘤重量比较,差异有统计学意义(F＝16.353,P=0.000).病理切片免疫组化结果显示,靶向-T3肽能明显减少与肿瘤血管生长相关的血管内皮生长因子的表达,降低肿瘤的侵袭能力,其效果优于T3肽.结论 靶向短肽介导的肿瘤抑素活性T3片段具有较强的骨肉瘤抑制能力,能够有效地富集在骨肉瘤血管内皮,具有低毒高效的治疗作用.%Objective To observe the inhibitory effect of tumstatin related peptide T3 mediated by short peptide to osteosarcoma vascular. Methods Through MTS assay, wound healing assay, the inhibitory effect of targeting-T3 peptide and T3 peptide on the human umbilical veil endothelial cell was studied in vitro. After the preparation of 50 nude mice model bearing osteosarcoma, the nude mice bearing too large or too small tumors were eliminated and the left ones were divided into 4 groups (6 animals for each group: T3 peptide, targeting-T3 peptide, CTX, PBS) randomly. Through weight of tumor, histopathologicol slice and immunohistochemical methods. The inhibitory action of targeting-T3 peptide and T3 peptide on the neoge-netic vascular of osteosarcoma implanted in nude mouse was studied. Results In vitro, both T3 peptide and targeting-T3 peptide effectively inhibited the proliferation of human umbilical veil endothelial cell. In the experiment of vivo, the average weight of tumor of targeting-T3 peptide group was (1.104?.247) g, the average weight of the T3 peptide group was (1.484?.369) g. There was the statistical difference in tumor inhibition on the osteosarcoma betweent the targeting-T3 group and T3 group (F=16.353, P=0.000). The positive rate of vascular endothelial growth factor and metastasis in the lung in the targeting-T3 peptide group all descended than the T3 peptide group. Conclusion Because of the short peptide to osteosarcoma vascular, targeting-T3 peptide could significantly restrain the development of osteosarcoma. Coupling short peptide to T3 peptide increase the selective binding of T3 peptide to osteosarcoma vascular.