牛磺酸对乳腺癌大鼠肿瘤生长、血浆代谢产物及相关基因表达的影响

摘要

Objective To investigate the effects of taurine on tumor growth,plasma metabolites and relevant genes expressions in rats with breast cancer.Methods Thirty female SD rats were randomly divided into control group,7,12-dimethylbenz[a]anthracene(DMBA) cancerigenic group,taurine intervention group,with 10 rats in each group.Intragastric administration of peanut oil(0.1 ml/kg) was conducted in the control group.And intragastric administration of 1.5 mg/ml DMBA solution(0.1 ml/kg) was conducted in the DMBA cancerigenic group and taurine intervention group.The daily drinking water was added with 6% taurine in the taurine intervention group.The incidence of breast tumors was observed in the three groups.The plasma metabolites of rats were detected then metabonomics analysis of metabolism was performed.Fluorescence quantitative PCR technology was used to detect the expressions of breast cancer related genes in breast cancer or normal breast tissues.Results Compared with the DMBA cancerigenic group,the amount of breast tumors was less and the latency was prolonged in the taurine group(P<0.05).Metabonomics analysis showed that the different metabolites between the taurine intervention group and the DMBA cancerigenic group mainly involved in the glucose metabolism and amino acid metabolism pathways.Compared with the control group,insulin-like growth factor 1 receptor(Igf1r) and phosphatase and tensin homolog deleted on chromosome 10(Pten) expressions decreased and insulin-like growth factor 1(Igf1) expression increased in the DMBA cancerigenic group(P<0.05).Compared with the DMBA cancerigenic group,Pten and Igf1r expressions increased and Igf1 expression decreased in the taurine intervention group(P<0.05).Conclusion Taurine acquires an inhibitory effect on the tumor growth in the rats with breast cancer induced by DMBA.This effect is likely related to the decreasing energy and nucleic acid metabolism caused by regulating relevant metabolism pathways and gene expression by taurine.%目的 探讨牛磺酸对乳腺癌大鼠肿瘤生长、血浆代谢产物及相关基因表达的影响.方法 将30只雌性SD大鼠随机分为对照组、7,12-二甲基苯蒽(DMBA)致癌组、牛磺酸干预组,每组10只.对照组给予花生油(0.1 ml/kg)灌胃,DMBA致癌组、牛磺酸干预组给予1.5 mg/ml DMBA溶液(0.1 ml/kg)灌胃,牛磺酸干预组于日常饮水中加入6%的牛磺酸.观察3组大鼠乳腺肿瘤发生情况,检测大鼠血浆代谢产物并进行代谢组学分析,用荧光定量PCR技术检测大鼠乳腺癌或正常乳腺组织乳腺癌相关基因表达.结果 与DMBA致癌组比较,牛磺酸干预组大鼠乳腺肿瘤数较少,潜伏期延长(P<0.05).代谢组学分析显示牛磺酸干预组与DMBA致癌组之间的差异代谢产物主要涉及糖代谢和氨基酸代谢通路.与对照组比较,DMBA致癌组胰岛素样生长因子受体1(Igf1r)、人第10号染色体缺失的磷酸酶及张力蛋白同源基因(Pten)表达降低,胰岛素样生长因子1(Igf1)基因表达升高(P<0.05);与DMBA致癌组比较,牛磺酸干预组Pten、Igf1r基因表达增加,Igf1基因表达降低(P<0.05).结论 牛磺酸对DMBA诱导的乳腺癌大鼠的肿瘤生长有抑制作用,这种作用很可能与牛磺酸通过调节相关代谢通路及基因表达从而降低能量代谢和核酸代谢有关.