蝎毒提取物抑制Lewis肺癌化疗期间再增殖实验研究

目的观察转移性Lewis肺癌在5-Fu化疗期间再增殖加速现象及蝎毒提取物(PESV)对再增殖的抑制作用。方法 C57BL/6小鼠尾iv Lewis肺癌细胞,从第7天开始,每隔7天ip 5-Fu 1次,建立Lewis肺癌化疗期间再增殖模型,以PESV干预,每隔7天处死6只动物,统计肺转移灶数目和肺质量,并以免疫组织化学方法检测Lewis肺癌增殖细胞核抗原(proliferating cell nuclear antigen,PCNA)、血管内皮生长因子(vascular endothelial growth factor,VEGF)表达水平和微血管密度(microvessel dentity,MVD)。结果模型组从第21天到第28天,大肿瘤转移灶数目平均增加2.5个,而从第14～21天仅平均增加0.8个;模型组肺质量增加在第21～28天显著大于第14～21天;模型组PCNA表达在第21天表达最低,在第28天最高,但第28天与第14天差异无显著性,PESV高、低剂量组在第28天表达水平皆低于模型组,以PESV高剂量组作用显著。模型组VEGF表达在第28天显著上调(与模型组第21天相比,P<0.01)。与模型组相比,PESV高剂量组在第21、28天肿瘤组织VEGF表达下调,尤其是在第28天表达显著下调(P<0.01),而PESV低剂量组仅在第28天与模型组差异存在显著性(P<0.05)。MVD计数显示,模型组在第21天最低,在第28天最高,但在第28天和第14天差异无显著性。而在PESV高剂量组,第14天高于第21天,第21天高于第28天,差异均有显著性。在PESV低剂量组,第14天高于第21天,但第21天与第28天差异无显著性。结论在5-Fu对Lewis肺癌化疗期间存在再增殖加速现象,PESV可有效抑制此Lewis肺癌再增殖,作用机制之一是通过抑制肿瘤新生血管生成来抑制肿瘤细胞再增殖。

Inhibition of polypeptide extract from scorpion venom on repopulation in Lewis lung adenocarcinoma during chemotherapy

Objective To identify the repopulation in metastatic Lewis lung adenocarcinoma during 5-Fu chemotherapy and observe the inhibition of polypeptide extract from scorpion venom (PESV) on the repopulation. Methods To make repopulation model, Lewis cells were iv injected into caudal vein of C57BL/6 mice, the mice were ip injected by 5-Fu once every 7 d since day 7 and intervened by ig administration of PESV. Groups were treated differently. Six mice were sacrificed every 7 d, with counting metastatic foci in lung and detecting the level of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and microvessel dentity (MVD) expression in Lewis lung metastatic loci by using immunohistochemistry. Results In model groups, from day 21 to day 28 the numbers of metastatic big loci increased 2.5 averagely, while from day 14 to day 21 increased 0.8 only; The weight of lung from day 21 to day 28 increased more than that from day 14 to day 21; The expression of PCNA was the lowest in day 21, the highest in day 28, and there was no significant difference between day 28 and day 14; The expression in both high- and low-dose PESV groups in day 28 was lower than that in model group. There was a significant effect in high-dose PESV group. In model group the expression of VEGF in day 28 was upregulated significantly (P<0.01 vs that in model group in day 21). Compared with model group, VEGF expression in high-dose PESV group in day 21 and day 28 was downregulated, especially in day 28 (P<0.01). In low-dose PESV group only in day 28 the difference was found (P<0.05 vs that in model group); The change of MVD was the same as PCNA. The expression was the lowest in day 21, the highest in day 28, and there was no significant difference between day 28 and day 14. While in high-dose PESV group, the number of MVD in day 14 was more than that in day 21, and in day 21 more than in day 28, there were significant differences. In low-dose PESV group, in day 14 more than in day 21, but no significant difference was found between day 21 and day 28. Conclusion The phenomenon of repopulation acceleration is found in Lewis lung adenocarcinoma during 5-Fu treatment and PESV could inhibit the repopulation through anti-angiogenesis which may be one of the mechanisms of inhibiting tumor cell repopulation.