南蛇藤提取物对人胃癌SGC-7901裸鼠移植瘤生长及凋亡相关蛋白表达的影响

Effect of Celastrus orbiculatus extract on growth and apoptosis-related protein expressions of human gastric adenocarcinoma SGC-7901 cell xenografts in nude mice

目的探讨南蛇藤茎醋酸乙酯提取物(COE)对人胃癌细胞SGC-7901裸鼠移植瘤生长及凋亡相关蛋白表达的影响。方法建立人胃癌裸鼠移植瘤模型,随机分为模型组,COE低、中、高剂量(10、20、40 mg/kg)组和希罗达(267 mg/kg)组,每组7只,各组ig给药,给药3周后检测裸鼠体质量、肿瘤体积、瘤质量等,绘制肿瘤生长曲线,并计算抑瘤率。应用TUNEL法检测COE处理后各组移植瘤组织中的细胞凋亡情况;免疫组织化学法和Western blotting技术分别检测各组移植瘤组织和SGC-7901肿瘤细胞中p53、Bcl-2、Bax蛋白的表达。结果 COE能够较好地抑制胃癌裸鼠移植瘤的生长,能明显缩小肿瘤体积,且呈剂量依赖性。COE低、中、高剂量组的抑瘤率分别为33.3%、46.8%、57.7%。TUNEL法显示COE处理后肿瘤细胞凋亡较模型组明显增多。免疫组化结果显示COE处理后移植瘤组织中p53和Bax蛋白表达有升高的趋势,而Bcl-2蛋白表达有降低的趋势。其中与模型组相比,COE高剂量组中p53和Bax蛋白表达显著升高(P<0.001),而Bcl-2蛋白表达显著降低(P<0.001)。Western blotting结果显示与免疫组化有大致相同的变化趋势。结论 COE对人胃癌细胞SGC-7901裸鼠移植瘤具有明显的抑制作用,其机制可能与上调p53和Bax的表达,下调Bcl-2的表达,诱导胃癌细胞凋亡有关。

Objective To explore the effects of Celastrus orbiculatus extract（COE） on the expressions of apoptosis-related proteins and growth of human gastric adenocarcinoma SGC-7901 cell xenografts in nude mice.Methods Thirty-five mice with subcutaneous xenografts of a gastric cancer cell line（SGC-7901） were randomly divided into five groups：a negative control group,a positive control group（xeloda）,and low-dose,medium-dose,and high-dose COE groups（10,20,and 40 mg/kg,respectively）.There were seven mice in each group.Tumor volume,tumor weight,and body weight were measured to draw up tumor growth curves and the tumor weight inhibition rates were calculated.The apoptosis rates were measured by TUNEL staining method and the expressions of p53,Bcl-2,and Bax proteins were detected by immunohistochemical staining and Western blotting assay.Results The COE could inhibit the growth of SGC-7901 xenografts in a dose-dependent manner.The tumor inhibitory rates were 33.3%,46.8%,and 57.7% when treated with 10,20,and 40 mg/kg COE,respectively.TUNEL assay showed that COE presented with apparently more apoptosis than the negative control group.The results of immunohistochemical staining showed the expressions of p53 and Bax proteins had a trend of up-regulation,while the expression of Bcl-2 protein had a trend of down-regulation in nude mice after treatment with COE.Compared with the negative control group,the expressions of p53 and Bax were significantly up-regulated,while the expression of Bcl-2 was down-regulated in the high-dose COE group.Western blotting analysis showed the similar results to immunohistochemical staining.Conclusion COE could significantly inhibit the growth of SGC-7901 cell xenografts in nude mice,which might be related with the up-regulation of the expressions of p53 and Bax and down-regulation of the expression of Bcl-2.