Mechanism study on the effect of androgen antagonism in prostate cancer
10.13263/j.cnki.nja.2023.05.003
- VernacularTitle:四羟基壬烯对前列腺癌雄激素拮抗作用的机制研究
- Author:
Xu SONG
1
;
Qiang SONG
;
Rong WANG
;
Qing-Jun ZUO
;
Zhi-Yuan ZHANG
Author Information
1. 上海中医药大学附属第七人民医院泌尿外科,上海 200137
- Keywords:
prostate cancer;
4-hydroxynonenal;
androgen antagonism;
androgen receptor-mitogen-activated protein kinases sig-naling pathway;
LNCaP cell
- From:
National Journal of Andrology
2023;29(5):402-408
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the mechanism of tetrahydroxynonene(4-HNE)in the androgen antagonistic effect of prostate cancer through the androgen receptor(AR)-mitogen activated protein kinase(MAPK)signaling pathway.Method:Prostate canc-er LNCaP cells were divided into wild-type group(NC,control group)and transfection group.The transfection group was further divid-ed into empty vector transfection group(NC-L7 group)and GSTA4 gene transfection group(A0718,GSTA4-OE group).The GSTA4-OE group received LNCaP cell culture and GSTA4 plasmid transfection to construct LNCaP stable 4-HNE cell lines,while the control group received LNCaP cell culture without GSTA4 plasmid transfection.Stimulating prostate cancer cells with different concentrations of 4-HNE(0,40,80,120μmol/L)to activate the AR signaling pathway,Western blot was used to detect the expression of AR,MAKp,AKT,and PKCα proteins.Sixty cases of prostate cancer tissues and sixty cases of benign prostatic hyperplasia tissues were selected.Immunohistochemical staining was used to determine the positive expression rate of 4-HNE in the aforementioned tissues.The correla-tion between the positive expression of 4-HNE and tumor Gleason grade,as well as the progression of prostate cancer to CRPC,was an-alyzed.Result:The level of 4-HNE in the GSTA4-OE group cells was inhibited.Western blot analysis showed that compared with the control group,the GSTA4-OE group had PKC in cells α The protein expression level significantly decreased(P＜0.05),while the expression levels of AR and AKT proteins significantly increased(P＜0.05).After treating prostate cancer cells with 40,80,and 120μmol/L 4-HNE,compared with the control group,the expression level of AKT in the treatment group was significantly reduced(P＜0.01),while the expression levels of MAKP(P＜0.01),PKC(P＜0.01),and AR(P＜0.01)were significantly increased.The immunohistochemical results showed that the positive rate of 4-HNE was 5.0％in 60 cases of benign prostatic hyperplasia tissue and 63.3％in 60 cases of prostate cancer tissue,with a statistically significant difference(P＜0.01).The positive rates of 4-HNE in Gl-eason grades 1-5 were 41.2％,50.0％,63.6％,81.8％,and 100.0％,respectively.The higher the Gleason grade,the higher the positive rate of 4-HNE,and the difference was statistically significant(P＜0.05).During a follow-up period of 10-35 months,33 pa-tients advanced to CRCP,while 27 patients did not.The positive expression rate of 4-HNE in the two groups showed a statistically sig-nificant difference(P＜0.01).Conclusion:Under the action of 4-HNE,the expression of AR-MAPK pathway related proteins in-crease.4-HNE may promote the progression of prostate cancer through the AR-MAPK pathway,and 4-HNE is expected to become a new therapeutic target for CRPC.
