The Significance Of The Ar/tmprss2-erg Fusion Gene Signaling Pathway In Targeted Treatment Of Prostate Cancer

Objective: Prostate cancer is a common male malignant tumor in Europe and the United States.The incidence rate of prostate cancer in Europe and the United States is higher than that in Asia.Androgen deprivation therapy is the main treatment for prostate cancer,but most patients have androgen resistance and androgen signal transduction is restored.TMPRSS2-ERG gene fusion exists in prostate cancer,and TMPRSS2-ERG gene fusion has been proved to regulate AR signal,so TMPRSS2-ERG gene fusion plays an important role in the occurrence and development of prostate cancer.This article takes AR and TMPRSS2-ERG as the target of treatment at the same time,and discusses the therapeutic effect on prostate cancer through the combination of AR inhibitor MDV3100 and ERG specific inhibitory polypeptide EIP.Methods: 1.In vitro experiments,the effect of drugs on the survival rate of VCaP cells was studied through both dose-effect and time-effect.In dose-effect,EIP and MDV3100 diluted with gradient concentration were used to calculate the survival rate with CCK8 after 72 hours of single or combined administration;CCK8 was used to calculate the survival rate after the fixed concentration of EIP and MDV3100 were administered separately or jointly for 0 h,24 h,48 h,72 h and 96 h.Flow cytometry was used to analyze the effect of single and combined drugs on VCaP cell apoptosis;Scratch test and Transwell were used to analyze the effects of single and combined drugs on the migration and invasion of VCaP cells;The expression of related genes and proteins in VCaP cells after EIP and MDV3100 were detected by q PCR and Western blot.2.In vivo experiment,VCaP cell subcutaneous prostate transplantation tumor model of combined immunodeficiency mice(Scid mice)was established.Through the use of EIP and MDV3100 alone or in combination,tumor volume,mouse weight and other indicators were measured to analyze the inhibitory effect of combined drugs on subcutaneous prostate transplantation tumor.Western blot and q PCR were used to detect the expression level of tumorigenesis related proteins and the transcription level of related genes.Results: 1.The combination of EIP and MDV3100 inhibited the viability of VCaP cells in a concentration and time dependent manner,and the two had synergistic effects.The combination of EIP and MDV3100 can promote the apoptosis of VCaP cells and inhibit the migration and invasion of VCaP cells.At the same time,the combination of EIP and MDV3100 down-regulates the expression of ERG,AR and other related genes and proteins.2.The combination of EIP and MDV3100 has inhibitory effect on subcutaneous prostate transplantation tumor in mice with combined immunodeficiency syndrome,and shows certain toxic and side effects;Reduce the expression of ERG protein and AR protein in tumor,and down-regulate the m RNA expression of TMPRSS2-ERG,ERG,AR,c-Myc,ADAM19,etc.Conclusion: The combination of EIP and MDV3100 can inhibit the survival rate of VCaP cells,promote cell apoptosis,inhibit cell migration and invasion,inhibit the expression of ERG,AR and other genes and proteins in cells,and inhibit the growth of subcutaneous transplanted tumor,which may become a strategy for the treatment of prostate cancer.