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

ABSTRACT

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.