褪黑素的抗胃癌效应及其对TNF-α、NO表达的调节作用

Anti-gastric cancer effect of melatonin and its regulatory effect on TNF-αand NO expression in vitro and in vivo

目的探讨褪黑素(melatonin,MLT)在体内外对胃癌细胞增殖活性的影响及其对肿瘤坏死因子-α(TNF-α)、一氧化氮(NO)表达的调节作用。方法构建不同浓度褪黑素干预皮下荷胃癌小鼠模型。测量各组小鼠肿瘤质量、体积;胸腺、脾脏指数;HE染色观察肿瘤组织形态;分离各组小鼠腹水巨噬细胞并计数分析。ELISA和比色法检测外周血清及腹水巨噬细胞培养液TNF-α、NO表达水平。不同浓度褪黑素干预小鼠胃癌细胞(MFC)。CCK-8检测各组MFC细胞的增殖活力;ELISA和比色法检测各组细胞培养上清TNF-α、NO表达水平。结果褪黑素干预后小鼠肿瘤质量、体积均显著下降,脾和胸腺指数无明显变化;相比对照组,褪黑素组外周血清和腹水巨噬细胞培养液TNF-α、NO表达水平均明显升高。褪黑素干预后MFC细胞增殖活力明显下降,呈剂量依赖性;同时,褪黑素组相比对照组MFC细胞上清NO表达降低,TNF-α表达升高。结论褪黑素体内外均能抑制胃癌细胞增殖活性,该作用与TNF-α表达上调、NO表达水平改变有关;也与体内巨噬细胞分泌TNF-α、NO水平增强有关。

Objective To investigate the effects of melatonin(MLT)on the proliferation of gastric cancer cells and its regulatory effect on the expression of tumor necrosis factor-α(TNF-α)and nitric oxide(NO)in vitro and in vivo.Methods Subcutaneous gastric cancer-bearing mouse models with different concentrations of melatonin intervention were established.Tumor weight and volume,thymus and spleen index were measured in each group;tumor morphology was observed by HE staining;ascites macrophages of each group were isolated and counted.The expression levels of TNF-αand NO in peripheral blood serum and ascites macrophage culture medium were detected by ELISA and colorimetry.Mouse foregastric carcinoma cell(MFC)model with the intervention of different concentrations of melatonin was constructed.The proliferation activity of MFC cells in each group was detected by CCK-8.The expression levels of TNF-αand NO in the supernatant of each group were detected by ELISA and colorimetry.Results The tumor weight and volume of mice were significantly decreased after melatonin intervention,and there was no significant change in spleen and thymus index.Compared with the control group,the expression levels of TNF-αand NO were increased significantly in both peripheral blood serum and ascites macrophage culture medium in melatonin group.The proliferation activity of MFC cells was significantly decreased after melatonin intervention in a dose-dependent manner,and the expression of NO was decreased but the expression of TNF-αwas increased in the melanin group compared with the control group. Conclusion Melatonin can inhibit the proliferation of gastric cancercells both in vitro and in vivo, which is related to the up-regulation of TNF-α expression and the change of NO expression level. It isalso related to the increased secretion of TNF-α and NO expression level in macrophages.