Based On The PI3K/AKT Signaling Pathway To Explore The Mechanism Of The Regulation Of Dioscorea Pill Combined With Cyclophosphamide In The Regulation Of Breast Cancer Epithelial-mesenchymal Transition(EMT)

Objective:To explore the effect and mechanism of dioscorea pill combined with cyclophosphamide on inhibiting tumor growth and epithelial-mesenchymal transition(EMT)in 4T1 breast cancer mice.Methods:Twenty-four 6-weeks-old BALB/c mice were randomly divided into a model group,a cyclophosphamide group,and a dioscorea pill combined with cyclophosphamide group.Each group of 8 mice was injected with 4T1 cell suspension to replicate the tumor-bearing model.After tumor formation,cyclophosphamide group was intraperitoneally injected with cyclophosphamide(100 mg/kg)once every 7 days for 21 days;dioscorea pill combined with cyclophosphamide group was given intraperitoneal injection of cyclophosphamide(100 mg / kg)and then daily The dioscorea pill(15ml/kg)was given by intragastric administration;the model group was given intraperitoneal injection of PBS and intragastric administration.During this period,the tumor volume of mice was measured every 3 days,and the tumor growth curve was drawn.After the treatment,the mice were sacrificed and the subcutaneous tumor-forming tissue was removed.Immunoblotting experiments were used to detect the protein expression levels of E-Cadherin,Vimentin,Akt and phosphorylated Akt(p-Akt)in mouse tumor tissues;RT-q PCR was used to detect E-Cadherin and Vimentin mRNA expression levels.Results:1.The 6th day after treatment: Compared with the model group,the tumor volume of the cyclophosphamide group and dioscorea pill combined with cyclophosphamide group was smaller,and the growth rate was slowed(P<0.05).From the 9th day after the treatment,the 12 th,15th,18 th and 21 st days:Compared with the model group,the tumor volume of the cyclophosphamide group,dioscorea pill combined with cyclophosphamide group is smaller,and the growth rate is slowed(P<0.05);compared with the cyclophosphamide group,the tumor volume of the cyclophosphamide combined with dioscorea pills group was smaller,and the growth rate was slowed(P<0.05).2.Western blot results showed that compared with the model group,the protein levels of Vimentin and p-Akt/Akt in the tumors of the cyclophosphamide group and dioscorea pill combined with cyclophosphamide group were significantly reduced(P<0.05),The expression level of E-cadherin was significantly increased(P<0.05).The dioscorea pill combined with cyclophosphamide group was more significantly changed than the cyclophosphamide group(P <0.05);3.RT-q PCR results showed that the mRNA expression level of Vimentin in mice tumors of cyclophosphamide group and dioscorea pill combined with cyclophosphamide group decreased(P <0.05),the mRNA expression level of E-cadherin increased(P <0.05),dioscorea pill combined with cyclophosphamide group had more significant changes than cyclophosphamide group(P <0.05).Conclusion:1.Dioscorea pill combined with cyclophosphamide is superior to cyclophosphamide in inhibiting tumor growth,indicating that Dioscores has a certain synergistic effect during breast cancer chemotherapy.2.Dioscores combined with cyclophosphamide can down-regulate p-Akt/Akt and Vimentin protein expression and mRNA expression in breast cancer tumors through PI3K/AKT signaling pathway,up-regulate E-cadherin protein and mRNA expression,prevent EMT progress,and thus prevent Has a certain inhibitory effect.