Shugan Jianpi Jiedu Formula Inhibits Gonadal Axis and PI3K/AKT/mTOR Signaling Pathways to Affect Breast Precancerous Lesions
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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