克拉霉素抑制肺癌细胞诱导血管内皮细胞迁移的实验研究

The inhibitory effect of clarithromycin on endothelial cell migration induced by lung cancer cell

目的 观察克拉霉素 (CAM)对人小细胞肺癌细胞表达VEGF其诱导血管内皮细胞迁移的影响 ,探讨CAM抗血管生成的机制。方法 采用免疫组化和图象分析技术 ,观察不同浓度的CAM作用下人小细胞肺癌细胞 (NCI -H4 4 6 )中VEGF蛋白表达的变化。采用共培养法 (Marigelinvasioncham ber) ,观察CAM对NCI -H4 4 6细胞诱导人血管内皮细胞(ECV - 30 4 )迁移的抑制作用。结果 CAM达到 30mmol/L对其诱导的ECV - 30 4细胞迁移表现出明显的抑制作用 ,达到 4 0mmol/L可以抑制NCI -H4 4 6细胞表达VEGF ,CAM浓度在 30、4 0和 5 0mmol/L时 ,抑制率分别为 19.7%、2 4 .3%和2 5 .0 % ,呈现出明显剂量—反应关系 (r =- 0 .76 4 ,P =0 .0 0 1)。结论 CAM能够抑制肺癌细胞诱导的血管内皮细胞迁移 ,对其表达VEGF也具有抑制作用 ,以上作用可能是CAM抗血管生成的机制之一。

Aim To investigate the effect of clarithromycin (CAM) on the migration of endothelial cells induced by lung cancer cells in vitro . Methods Cells of human umbilical vein endothelial cell line (ECV-304) and human small cell lung cancer cell line (NCI-H446) were cocultured in Marigel invasion chamber system, and the effect of CAM on the migration of ECV-304 induced by NCI-H446 was investigated. The VEGF expression in NCI-H446 was examined by immunohistochemical staining and image analysis. Results The expression of VEGF in NCI-H446 cells was reduced after treatment with 40 mmol/L CAM. CAM at concentration of over 30 mmol/L significantly inhibited the chemoactic migration of ECV-304 cells induced by NCI-H446 cells in a dose-dependent manner. Conclusion The results confirm the inhibitory effects of CAM on the endothelial cells migration induced by lung cancer cells and VEGF expression in lung cancer cells suggesting that CAM can suppress angiogenesis and has possible therapeutic applications.