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蝎毒多肽提取物对化疗期间H22肿瘤细胞再增殖的抑制作用

[Inhibitive effect of polypeptide extract from scorpion venom on repopulation in H22 tumor cell during chemotherapy].

作者信息

Wang Zhaopeng, Zhang Weidong, Jia Qing, Wang Zhaoxia, Zhang Yueying, Wang Yan

机构信息

Dept of pathology, Institute of Basic Medcine, Shandong Academy of Medical Science, Key Laboratory for Modern Medicine and Technology of Shandong Province, Jinan 250062, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2010 Jan;35(1):108-13.

Abstract

OBJECTIVE

To observe the inhabitive effect and mechanism of polypeptide extract from scorpion venom (PESV) on repopulation in H22 tumor cell during chemotherapy.

METHOD

H22 tumor cells were injected into 96 mice subcutaneously, then mice were divided into 4 groups radomly: Model, low-dose-PESV, high-dose-PESV, and control. Reppulation model was established by 5-Fu treating mice with H22. Four groups was treated differently, 6 mice of each group was sacrificed every 7 days, measured tumor volume twice one week. The expression of vascular endothelial growth factor (VEGF), proliferating cell nuclear antigen (PCNA), CD105 microvessel density (CD105-MVD) and platelet derived growth factor (PDGF) in H22 tumor issue was observed by using immunohistochemistry and grey analysis, the relation of VEGF and MVD was affirmed by correlation analysis.

RESULT

In control group tumor volume of H22 increased quickly in 13-24 day, and all mice died before 27 day. In model tumor volume increased quickly before 17, in 17-22 day slowly, after 22 day quickly again, and all the mice died before 31 day. In low and high dose PESV, tumor volume added slowly, and only in 17 day there was significant difference between these two groups. Immunohistochemistry showed, PCNA expression of model group in 31 day was higher than in 21, 28 day, the expression level of high and low PESV group was lower than model group all the time, only in 17 day there was significant difference between high and low PESV group. Immunohistochemitry showed, compared with high and low dose PESV group, CD105-MVD of model group was higher in 21, 28 day (P < 0.05) and in 35 day (P < 0.01), and no difference was found between high and low dose PESV. VEGF expression of model group in 35 day was higher than in 21, 28 day (P < 0.01), and model group higher than high and low dose PESV in 21, 28, 35 day. The expression of PDGF in model decreased gradually, in high and low dose PESV, the expression was lowest in 21 day. In day 35 high dose PESV higher than low dose PESV. There was positive correlation (r = 0.669) between VEGF expression and CD105-MVD.

CONCLUSION

PESV can inhabit repopulation of H22 tumor cell during chemotherapy, and the mechanism maybe is through anti-angiogenesis and nomalizing tumor vessels.

摘要

目的

观察蝎毒多肽提取物(PESV)对化疗期间H22肿瘤细胞再增殖的抑制作用及机制。

方法

将H22肿瘤细胞皮下接种于96只小鼠,然后随机分为4组:模型组、低剂量PESV组、高剂量PESV组和对照组。通过5-氟尿嘧啶处理荷H22小鼠建立再增殖模型。4组处理方式不同,每组6只小鼠,每7天处死一批,每周测量2次肿瘤体积。采用免疫组织化学及灰度分析观察H22肿瘤组织中血管内皮生长因子(VEGF)、增殖细胞核抗原(PCNA)、CD105微血管密度(CD105-MVD)和血小板衍生生长因子(PDGF)的表达,通过相关性分析确定VEGF与MVD的关系。

结果

对照组H22肿瘤体积在13 - 24天迅速增大,所有小鼠在27天前死亡。模型组肿瘤体积在17天前迅速增大,17 - 22天缓慢增大,22天后又迅速增大,所有小鼠在31天前死亡。低剂量和高剂量PESV组肿瘤体积增长缓慢,仅在17天两组间有显著差异。免疫组织化学显示,模型组31天PCNA表达高于21天、28天,高、低剂量PESV组表达水平始终低于模型组,仅在17天高、低剂量PESV组间有显著差异。免疫组织化学显示,与高、低剂量PESV组相比,模型组21天、28天(P < 0.05)及35天(P < 0.01)的CD105-MVD更高,高、低剂量PESV组间无差异。模型组35天VEGF表达高于21天、28天(P < 0.01),且在21天、28天、35天模型组高于高、低剂量PESV组。模型组PDGF表达逐渐降低,高、低剂量PESV组在21天表达最低。35天高剂量PESV高于低剂量PESV。VEGF表达与CD105-MVD呈正相关(r = 0.669)。

结论

PESV可抑制化疗期间H22肿瘤细胞的再增殖,其机制可能是通过抗血管生成和使肿瘤血管正常化。

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