摘要
目的 研究疏肝健脾解毒方通过调节磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)通路和性腺轴来逆转大鼠乳腺癌前病变的分子机制.方法 将60只SD雌性大鼠随机分为6组:空白组,乳腺癌前病变模型组(模型组),疏肝健脾解毒方低、中、高剂量组,他莫昔芬组,每组10只.采用二甲基苯蒽(DMBA)造模法造模.实验第1天用溶解有DMBA的芝麻油(10mg/mL),按100 mg/kg给予大鼠一次性灌胃处理.ELISA检测卵泡刺激素(FSH)、黄体生成素(LH)、泌乳素(PRL)、孕酮(P)、睾酮(T)及雌二醇(E2);RT-PCR检测雌激素受体(ER)、PI3K、Akt及mTOR的mRNA表达水平.结果 与模型组比较,疏肝健脾解毒方各剂量组及他莫昔芬组体质量升高(P＜0.05),卵巢和子宫系数均降低(P＜0.05),FSH、LH、PRL、P、T、E2、ER mRNA、PI3K mRNA、Akt mRNA及mTOR mRNA表达量均降低(P＜0.05).与疏肝健脾解毒方低剂量组比较,疏肝健脾解毒方中、高剂量组体质量升高(P＜0.05),子宫与卵巢系数降低(P＜0.05);疏肝健脾解毒方高剂量组FSH、LH、PRL、P、T、E2降低(P＜0.05),ER、PI3K、Akt、mTOR mRNA表达量降低(P＜0.05).与他莫昔芬组比较,中药高剂量组子宫与卵巢系数小幅度升高(P＜0.05).结论 疏肝健脾解毒方可能通过对性腺轴的抑制,使ER的表达下降,从而抑制PI3K/Akt/mTOR信号通路的表达,逆转了乳腺癌前病变,其作用效果随着中药剂量增高而加强.
Abstract
Objective To study the molecular mechanism of Shugan Jianpi Jiedu Formula(SJJF)in reversing precancerous lesion of breast cancer in rats by regulating phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)pathway and gonadal axis.Methods Sixty female SD rats were randomly divided into 6 groups,i.e.,blank group,breast precancerous lesion model group,SJJF with low dose group,middle dose group,high dose group and tamoxifen group,with 10 rats in each group.Dimethylbenzanthrene(DMBA)modeling method was used.On the first day of the experiment,sesame oil(10 mg/mL)dissolved with DMBA was given to the rats by gavage at a dose of 100 mg/kg.ELISA was used to detect follicle stimulating hormone(FSH),luteinizing hormone(LH),prolactin(PRL),progesterone(P),testosterone(T)and estradiol(E2).RT-PCR was used to detect the mRNA expression of(estrogen receptor)ER,PI3K mRNA,Akt,and mTOR.Results Compared with the model group,the body weight of each dose of SJJF groups and tamoxifen group increased(P＜0.05),while the ovarian and uterine coefficients decreased(P＜0.05).The expression levels of FSH,LH,PRL,P,T,E2,ER mRNA,PI3K mRNA,Akt mRNA,and mTOR mRNA decreased(P＜0.05).Compared with the low dose group,the body weight of the middle dose group and the high dose group increased(P＜0.05);the uterine and ovarian coefficients decreased(P＜0.05);the high dose group showed a decrease in FSH,LH,PRL,P,T,and E2(P＜0.05);while the expression of ER,PI3K,Akt,and mTOR mRNA decreased(P＜0.05).Compared with the tamoxifen group,the uterine and ovarian coefficients in the high dose group increased(P＜0.05).Conclusions SJJF may reduce the expression of ER by inhibiting the gonadal axis,thereby inhibiting the expression of PI3K/AKT/mTOR signaling pathway,and reversing precancerous lesions of breast cancer.Its effect was enhanced with the increase of Chinese herbal medicine dosage.
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