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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。
Objective To observe the accelerated proliferation of metastatic Lewis lung carcinoma (NSCLC) during 5-Fu chemotherapy and the inhibitory effect of extract of scorpion venom (PESV) on re-proliferation. Methods C57BL / 6 mice were transplanted with iv Lewis lung cancer cells. From day 7, ip 5-Fu was administered once every 7 days to establish a model of repopulation of Lewis lung carcinoma during chemotherapy. Six animals were sacrificed every 7 days with PESV intervention , The number of lung metastases and the quality of lungs were detected. The expression of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF) and microvessel in Lewis lung carcinoma were detected by immunohistochemistry dentity, MVD). Results In the model group, the number of large tumor metastases increased by an average of 2.5 days from the 21st day to the 28th day, while it increased by only 0.8 from the 14th to 21st days on average. In the model group, the lung mass increased significantly from the 14th to the 28th days ~ 21 days. The expression of PCNA in the model group was the lowest on the 21st day, the highest on the 28th day, but the difference was not significant on the 28th day and the 14th day. The expression level of PCNA in model group was lower than that on the 28th day Group, PESV high-dose group significant effect. The expression of VEGF in model group was significantly increased on the 28th day (P <0.01 compared with the 21th day in the model group). Compared with the model group, VEGF expression was down-regulated in the high-dose PESV group on the 21st and 28th day, especially on the 28th day (P <0.01), while the low-dose PESV group was only associated with the model group The difference was significant (P <0.05). The MVD count showed that the model group was the lowest on the 21st day and the highest on the 28th day, but the difference was not significant on the 28th and the 14th day. In the PESV high-dose group, the difference was significant between the 14th day and the 21st day, and the 21st day was higher than the 28th day. In the PESV low-dose group, the 14th day was higher than the 21st day, but there was no significant difference between the 21st day and the 28th day. Conclusions 5-Fu accelerates the proliferation of Lewis lung carcinoma during chemotherapy. PESV can effectively inhibit the re-proliferation of Lewis lung carcinoma. One of the mechanisms is that PESV inhibits the proliferation of Lewis lung carcinoma by inhibiting tumor angiogenesis.