Abstract:
Objective:To investigate the effect of simvastatin on prol i feration and nuclear factor kappa B (NF κ B) expres-sion in the esophageal cancer (EsC) cell EC 9706. Methods:The human esophageal cancer cell line EC9706was cultured. MTT assay was used to determine the effect of simvastatin on the proliferation of EC9706cells at different concentrations. Morphological changes of the cells were observed by transmission electron microscopy and laser scanning confocal mi-croscopy. Flow cytometry was used to detect the effect of simvastatin on the apoptotic rates and cell cycle distribution, and immunocytochemistry was conducted to investigate the effect of the drug on expression of NF-κ B in the EC9706cells. Results: It was confirmed by MTT assay that within the concentration interval of 0~20μ mol /L, as the concentration and expo-sure time were increased, the inhibition ratio of simvastatin on the EsC cell EC 9706 gradually increased. It could be seen by transmission electron microscopy and laser scanning confocal microscopy that the typical morphological change ofapoptosis occurred in the cells. Flow cytometry was used to detect the apoptotic rate, and the cell cycle was blocked at the phase G 0/G1. Cells were exposed to simvastatin at increasing concentrations ( 0, 5, 10, 20μ mol /L) for 72h and positive rates of the NF-κ B nuclear staining were observed (46.2 ± 5.0, 38.3 ± 4.8b, 30.8 ± 4.0b, 23.4 ± 2.1b %) (a P<0.05, b P<00.01vs. control group). After exposure to 20μ mol /L of simvastatin for increasing times (0, 24, 48and 72h), the positive rates of NF-κ B nuclear staining decreased (37.8 ± 2.8, 31.6 ± 2.6a, 25.6 ± 2.2b, 16.8 ± 2.0b) (aP<00.05, b P<00.01vs. control group). Wi th an increase of the concentration and extension of the time of simvastatin exposure, the NF-κ B expres-sion in the EsC cell EC9706 gradually decreased. Conclusion:Simvastatin significantly inhibits the proliferation of EsC cell EC9706and there is a positive correlation between the concentration and effectiveness of the drug. This mechanism of ac-tion might be related to the apoptosis resul ting from inhibi tion of NF-κB expression in the EC9706cells.