肿瘤抑素抗血管活性相关肽对宫颈癌Hela细胞生长和转移抑制作用的实验研究

Inhibition of growth and metastasis of human cervical carcinoma cell implanted in nude mice by recombinant anti-angiogenic peptides of tumstatin

目的研究改造后的血管生成抑制相关肽(21肽)抗血管生成活性及对人宫颈癌Hela细胞皮下移植裸鼠模型的抑制作用,探讨其抑瘤作用机制。方法2005年8月至2006年2月哈尔滨医科大学第一临床医学院进行Hela细胞株皮下接种裸鼠造模,21肽治疗3周后,处死动物剥离肿瘤,称重并计算抑瘤率。免疫组化方法检测21肽对肿瘤组织的微血管密度(MVD)、增殖细胞核抗原(PCNA)和血管内皮生长因子(VEGF)的影响。结果21肽组平均抑瘤率可达51.89%,肿瘤组织微血管密度明显降低,与对照组比较差异有统计学意义(P<0.05);21肽组肿瘤组织的PCNA、VEGF呈低表达,与对照组比较差异有统计学意义(P<0.05)。结论21肽具有显著的抗血管生成活性,可明显地抑制裸鼠宫颈癌细胞的生长,其抑制宫颈癌的作用机制可能与其降低新生血管形成和调解血管生成相关因子的表达有关。

Objective To study the biological activity of recombinant anti-angiogenic peptides of tumstatin （21 Peptides） and its inhibitory action on the growth and metastasis of human cervical carcinoma cell （Hela） implanted in nude mice, and to investigate into the mechanism of its inhibitory action. Methods The human cervical carcinoma cell line Hela was implanted subcutaneously in nude mice. The 21 peptides were administered for twenty-one days. Then mice were killed, tumors were weighed and the restrained percentage of tumor were calculated. In addition, the microvessel density （MVD） ,the positive rate of vascular endothelial growth factor （VEGF） and the proliferating cell nuclear antigen （PCNA） index were detected by immunohistochemical methods. Results In 21 peptides group, the restrained percentage of tumor was 51.89%. The MVD, expression of the PCNA index and the positive rate of VEGF in 21 peptides group all descended （ all P 〈 0. 05 ）. Conclusion The above data indicate that the 21 peptides can significantly restrain the development of mice cervical cancer. The mechanism may be relevant to its effects of antiangiogensis and decreasing proliferation.